Orchestration of antiviral responses within the infected central nervous system.
Microglia activation
T cell recruitment to the brain
Virus control within the brain
Virus infection
Journal
Cellular & molecular immunology
ISSN: 2042-0226
Titre abrégé: Cell Mol Immunol
Pays: China
ID NLM: 101242872
Informations de publication
Date de publication:
12 Jul 2024
12 Jul 2024
Historique:
received:
29
03
2024
accepted:
05
05
2024
medline:
13
7
2024
pubmed:
13
7
2024
entrez:
12
7
2024
Statut:
aheadofprint
Résumé
Many newly emerging and re-emerging viruses have neuroinvasive potential, underscoring viral encephalitis as a global research priority. Upon entry of the virus into the CNS, severe neurological life-threatening conditions may manifest that are associated with high morbidity and mortality. The currently available therapeutic arsenal against viral encephalitis is rather limited, emphasizing the need to better understand the conditions of local antiviral immunity within the infected CNS. In this review, we discuss new insights into the pathophysiology of viral encephalitis, with a focus on myeloid cells and CD8
Identifiants
pubmed: 38997413
doi: 10.1038/s41423-024-01181-7
pii: 10.1038/s41423-024-01181-7
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 398066876/GRK 2485/1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : EXC 2155 "RESIST"-Project ID 39087428
Organisme : Helmholtz Association
ID : Zukunftsthema "Immunology & Inflammation" (ZT-0027)
Informations de copyright
© 2024. The Author(s).
Références
Venkatesan A, Michael BD, Probasco JC, Geocadin RG, Solomon T. Acute encephalitis in immunocompetent adults. Lancet. 2019;393:702–16. https://doi.org/10.1016/S0140-6736(18)32526-1 .
doi: 10.1016/S0140-6736(18)32526-1
pubmed: 30782344
Kennedy PG. Viral encephalitis: causes, differential diagnosis, and management. J Neurol Neurosurg Psychiatry. 2004;75(Suppl 1):i10–15. https://doi.org/10.1136/jnnp.2003.034280 .
doi: 10.1136/jnnp.2003.034280
pubmed: 14978145
pmcid: 1765650
Armangue T, Spatola M, Vlagea A, Mattozzi S, Cárceles-Cordon M, Martinez-Heras E, et al. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol. 2018;17:760–72. https://doi.org/10.1016/S1474-4422(18)30244-8 .
doi: 10.1016/S1474-4422(18)30244-8
pubmed: 30049614
pmcid: 6128696
Fooks AR, Banyard AC, Horton DL, Johnson N, McElhinney LM, Jackson AC. Current status of rabies and prospects for elimination. Lancet. 2014;384:1389–99. https://doi.org/10.1016/S0140-6736(13)62707-5 .
doi: 10.1016/S0140-6736(13)62707-5
pubmed: 24828901
pmcid: 7159301
Turtle L, Solomon T. Japanese encephalitis—the prospects for new treatments. Nat Rev Neurol. 2018;14:298–313. https://doi.org/10.1038/nrneurol.2018.30 .
doi: 10.1038/nrneurol.2018.30
pubmed: 29697099
Kramer LD, Li J, Shi PY. West Nile virus. Lancet Neurol. 2007;6:171–81. https://doi.org/10.1016/S1474-4422(07)70030-3 .
doi: 10.1016/S1474-4422(07)70030-3
pubmed: 17239804
Carod-Artal FJ, Wichmann O, Farrar J, Gascon J. Neurological complications of dengue virus infection. Lancet Neurol. 2013;12:906–19. https://doi.org/10.1016/S1474-4422(13)70150-9 .
doi: 10.1016/S1474-4422(13)70150-9
pubmed: 23948177
Cain MD, Salimi H, Diamond MS, Klein RS. Mechanisms of pathogen invasion into the central nervous system. Neuron. 2019;103:771–83. https://doi.org/10.1016/j.neuron.2019.07.015 .
doi: 10.1016/j.neuron.2019.07.015
pubmed: 31487528
Dai J, Wang P, Bai F, Town T, Fikrig E. Icam-1 participates in the entry of west nile virus into the central nervous system. J Virol. 2008;82:4164–8. https://doi.org/10.1128/JVI.02621-07 .
doi: 10.1128/JVI.02621-07
pubmed: 18256150
pmcid: 2292986
Bai F, Kong KF, Dai J, Qian F, Zhang L, Brown CR, et al. A paradoxical role for neutrophils in the pathogenesis of West Nile virus. J Infect Dis. 2010;202:1804–12. https://doi.org/10.1086/657416 .
doi: 10.1086/657416
pubmed: 21050124
pmcid: 3053000
Taylor MP, Enquist LW. Axonal spread of neuroinvasive viral infections. Trends Microbiol. 2015;23:283–8. https://doi.org/10.1016/j.tim.2015.01.002 .
doi: 10.1016/j.tim.2015.01.002
pubmed: 25639651
pmcid: 4417403
Papa MP, Meuren LM, Coelho S, Lucas C, Mustafá YM, Lemos Matassoli F, et al. Zika virus infects, activates, and crosses brain microvascular endothelial cells, without barrier disruption. Front Microbiol. 2017;8:2557. https://doi.org/10.3389/fmicb.2017.02557 .
doi: 10.3389/fmicb.2017.02557
pubmed: 29312238
pmcid: 5743735
Hasebe R, Suzuki T, Makino Y, Igarashi M, Yamanouchi S, Maeda A, et al. Transcellular transport of West Nile virus-like particles across human endothelial cells depends on residues 156 and 159 of envelope protein. BMC Microbiol. 2010;10:165. https://doi.org/10.1186/1471-2180-10-165 .
doi: 10.1186/1471-2180-10-165
pubmed: 20529314
pmcid: 2889955
Hosseini S, Wilk E, Michaelsen-Preusse K, Gerhauser I, Baumgärtner W, Geffers R, et al. Long-term neuroinflammation induced by influenza A virus infection and the impact on hippocampal neuron morphology and function. J Neurosci. 2018;38:3060–80. https://doi.org/10.1523/JNEUROSCI.1740-17.2018 .
doi: 10.1523/JNEUROSCI.1740-17.2018
pubmed: 29487124
pmcid: 6596076
Kalinke U, Bechmann I, Detje CN. Host strategies against virus entry via the olfactory system. Virulence. 2011;2:367–70. https://doi.org/10.4161/viru.2.4.16138 .
doi: 10.4161/viru.2.4.16138
pubmed: 21758005
Bauer L, Laksono BM, de Vrij F, Kushner SA, Harschnitz O, van Riel D. The neuroinvasiveness, neurotropism, and neurovirulence of SARS-CoV-2. Trends Neurosci. 2022;45:358–68. https://doi.org/10.1016/j.tins.2022.02.006 .
doi: 10.1016/j.tins.2022.02.006
pubmed: 35279295
pmcid: 8890977
Koyuncu OO, Perlman DH, Enquist LW. Efficient retrograde transport of pseudorabies virus within neurons requires local protein synthesis in axons. Cell Host Microbe. 2013;13:54–66. https://doi.org/10.1016/j.chom.2012.10.021 .
doi: 10.1016/j.chom.2012.10.021
pubmed: 23332155
pmcid: 3552305
Cain MD, Klein NR, Jiang X, Salimi H, Wu Q, Miller MJ, et al. Post-exposure intranasal IFNalpha suppresses replication and neuroinvasion of Venezuelan Equine Encephalitis virus within olfactory sensory neurons. J Neuroinflamm. 2024;21:24. https://doi.org/10.1186/s12974-023-02960-1 .
doi: 10.1186/s12974-023-02960-1
Ma H, Kim AS, Kafai NM, Earnest JT, Shah AP, Case JB, et al. LDLRAD3 is a receptor for Venezuelan equine encephalitis virus. Nature. 2020;588:308–14. https://doi.org/10.1038/s41586-020-2915-3 .
doi: 10.1038/s41586-020-2915-3
pubmed: 33208938
pmcid: 7769003
Finkelshtein D, Werman A, Novick D, Barak S, Rubinstein M. LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus. Proc Natl Acad Sci USA. 2013;110:7306–11. https://doi.org/10.1073/pnas.1214441110 .
doi: 10.1073/pnas.1214441110
pubmed: 23589850
pmcid: 3645523
Shivkumar M, Milho R, May JS, Nicoll MP, Efstathiou S, Stevenson PG. Herpes simplex virus 1 targets the murine olfactory neuroepithelium for host entry. J Virol. 2013;87:10477–88. https://doi.org/10.1128/JVI.01748-13 .
doi: 10.1128/JVI.01748-13
pubmed: 23903843
pmcid: 3807398
Menasria R, Boivin N, Lebel M, Piret J, Gosselin J, Boivin G. Both TRIF and IPS-1 adaptor proteins contribute to the cerebral innate immune response against herpes simplex virus 1 infection. J Virol. 2013;87:7301–8. https://doi.org/10.1128/JVI.00591-13 .
doi: 10.1128/JVI.00591-13
pubmed: 23596298
pmcid: 3700287
Menendez CM, Carr DJJ. Herpes simplex virus-1 infects the olfactory bulb shortly following ocular infection and exhibits a long-term inflammatory profile in the form of effector and HSV-1-specific T cells. J Neuroinflamm. 2017;14:124. https://doi.org/10.1186/s12974-017-0903-9 .
doi: 10.1186/s12974-017-0903-9
Detje CN, Lienenklaus S, Chhatbar C, Spanier J, Prajeeth CK, Soldner C, et al. Upon intranasal vesicular stomatitis virus infection, astrocytes in the olfactory bulb are important interferon Beta producers that protect from lethal encephalitis. J Virol. 2015;89:2731–8. https://doi.org/10.1128/JVI.02044-14 .
doi: 10.1128/JVI.02044-14
pubmed: 25540366
Pfefferkorn C, Kallfass C, Lienenklaus S, Spanier J, Kalinke U, Rieder M, et al. Abortively infected astrocytes appear to represent the main source of interferon beta in the virus-infected brain. J Virol. 2016;90:2031–8. https://doi.org/10.1128/JVI.02979-15 .
doi: 10.1128/JVI.02979-15
pubmed: 26656686
pmcid: 4733997
Detje CN, Meyer T, Schmidt H, Kreuz D, Rose JK, Bechmann I, et al. Local type I IFN receptor signaling protects against virus spread within the central nervous system. J Immunol. 2009;182:2297–304. https://doi.org/10.4049/jimmunol.0800596 .
doi: 10.4049/jimmunol.0800596
pubmed: 19201884
Chhatbar C, Detje CN, Grabski E, Borst K, Spanier J, Ghita L, et al. Type I interferon receptor signaling of neurons and astrocytes regulates microglia activation during viral encephalitis. Cell Rep. 2018;25:118–29.e114. https://doi.org/10.1016/j.celrep.2018.09.003 .
doi: 10.1016/j.celrep.2018.09.003
pubmed: 30282022
pmcid: 7103936
Nayak D, Johnson KR, Heydari S, Roth TL, Zinselmeyer BH, McGavern DB. Type I interferon programs innate myeloid dynamics and gene expression in the virally infected nervous system. PLoS Pathog. 2013;9:e1003395. https://doi.org/10.1371/journal.ppat.1003395 .
doi: 10.1371/journal.ppat.1003395
pubmed: 23737750
pmcid: 3667771
Moseman, EA, Blanchard, AC, Nayak, D & McGavern, DB T cell engagement of cross-presenting microglia protects the brain from a nasal virus infection. Sci Immunol. 2020;5. https://doi.org/10.1126/sciimmunol.abb1817 .
Ghita L, Breitkopf V, Mulenge F, Pavlou A, Gern OL, Durán V, et al. MyD88 signaling by neurons induces chemokines that recruit protective leukocytes to the virus-infected CNS. Sci Immunol. 2021;6:eabc9165. https://doi.org/10.1126/sciimmunol.abc9165 .
doi: 10.1126/sciimmunol.abc9165
pubmed: 34172587
pmcid: 8717402
Xydakis MS, Albers MW, Holbrook EH, Lyon DM, Shih RY, Frasnelli JA, et al. Post-viral effects of COVID-19 in the olfactory system and their implications. Lancet Neurol. 2021;20:753–61. https://doi.org/10.1016/S1474-4422(21)00182-4 .
doi: 10.1016/S1474-4422(21)00182-4
pubmed: 34339626
pmcid: 8324113
Meinhardt J, Radke J, Dittmayer C, Franz J, Thomas C, Mothes R, et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci. 2021;24:168–75. https://doi.org/10.1038/s41593-020-00758-5 .
doi: 10.1038/s41593-020-00758-5
pubmed: 33257876
Zheng J, Wong LR, Li K, Verma AK, Ortiz ME, Wohlford-Lenane C, et al. COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice. Nature. 2021;589:603–7. https://doi.org/10.1038/s41586-020-2943-z .
doi: 10.1038/s41586-020-2943-z
pubmed: 33166988
Verma, AK, Zheng, J, Meyerholz, DK & Perlman, S SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways. JCI Insight. 2022;7. https://doi.org/10.1172/jci.insight.160277 .
Soung AL, Vanderheiden A, Nordvig AS, Sissoko CA, Canoll P, Mariani MB, et al. COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis. Brain. 2022;145:4193–201. https://doi.org/10.1093/brain/awac270 .
doi: 10.1093/brain/awac270
pubmed: 36004663
pmcid: 9452175
Fernández-Castañeda A, Lu P, Geraghty AC, Song E, Lee MH, Wood J, et al. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell. 2022;185:2452–68.e2416. https://doi.org/10.1016/j.cell.2022.06.008 .
doi: 10.1016/j.cell.2022.06.008
pubmed: 35768006
pmcid: 9189143
Xu E, Xie Y, Al-Aly Z. Long-term neurologic outcomes of COVID-19. Nat Med. 2022;28:2406–15. https://doi.org/10.1038/s41591-022-02001-z .
doi: 10.1038/s41591-022-02001-z
pubmed: 36138154
pmcid: 9671811
Dupuis S, Jouanguy E, Al-Hajjar S, Fieschi C, Al-Mohsen IZ, Al-Jumaah S, et al. Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nat Genet. 2003;33:388–91. https://doi.org/10.1038/ng1097 .
doi: 10.1038/ng1097
pubmed: 12590259
Bastard P, Manry J, Chen J, Rosain J, Seeleuthner Y, AbuZaitun O, et al. Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency. J Clin Investig. 2021;131:e139980. https://doi.org/10.1172/JCI139980 .
doi: 10.1172/JCI139980
pubmed: 32960813
pmcid: 7773360
Bravo García-Morato M, Calvo Apalategi A, Bravo-Gallego LY, Blázquez Moreno A, Simón-Fuentes M, Garmendia JV, et al. Impaired control of multiple viral infections in a family with complete IRF9 deficiency. J Allergy Clin Immunol. 2019;144:309–12. https://doi.org/10.1016/j.jaci.2019.02.019 . e310
doi: 10.1016/j.jaci.2019.02.019
pubmed: 30826365
Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370:eabd4585. https://doi.org/10.1126/science.abd4585 .
doi: 10.1126/science.abd4585
pubmed: 32972996
pmcid: 7857397
Gervais A, Rovida F, Avanzini MA, Croce S, Marchal A, Lin SC, et al. Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in approximately 40% of patients. J Exp Med. 2023;220:e20230661. https://doi.org/10.1084/jem.20230661 .
doi: 10.1084/jem.20230661
pubmed: 37347462
pmcid: 10287549
Rosa JS, Kappagoda S, Hsu AP, Davis J, Holland SM, Liu AY. West Nile virus encephalitis in GATA2 deficiency. Allergy Asthma Clin Immunol. 2019;15:5. https://doi.org/10.1186/s13223-019-0321-x .
doi: 10.1186/s13223-019-0321-x
pubmed: 30697248
pmcid: 6346581
Weber F, Wagner V, Rasmussen SB, Hartmann R, Paludan SR. Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses. J Virol. 2006;80:5059–64. https://doi.org/10.1128/JVI.80.10.5059-5064.2006 .
doi: 10.1128/JVI.80.10.5059-5064.2006
pubmed: 16641297
pmcid: 1472073
Tabeta K, Hoebe K, Janssen EM, Du X, Georgel P, Crozat K, et al. The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Nat Immunol. 2006;7:156–64. https://doi.org/10.1038/ni1297 .
doi: 10.1038/ni1297
pubmed: 16415873
Casrouge A, Zhang SY, Eidenschenk C, Jouanguy E, Puel A, Yang K, et al. Herpes simplex virus encephalitis in human UNC-93B deficiency. Science. 2006;314:308–12. https://doi.org/10.1126/science.1128346 .
doi: 10.1126/science.1128346
pubmed: 16973841
Kim YM, Brinkmann MM, Paquet ME, Ploegh HL. UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes. Nature. 2008;452:234–8. https://doi.org/10.1038/nature06726 .
doi: 10.1038/nature06726
pubmed: 18305481
Lee BL, Moon JE, Shu JH, Yuan L, Newman ZR, Schekman R, Barton GM. UNC93B1 mediates differential trafficking of endosomal TLRs. Elife. 2013;2:e00291. https://doi.org/10.7554/eLife.00291 .
doi: 10.7554/eLife.00291
pubmed: 23426999
pmcid: 3576711
Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, Romero P, et al. TLR3 deficiency in patients with herpes simplex encephalitis. Science. 2007;317:1522–7. https://doi.org/10.1126/science.1139522 .
doi: 10.1126/science.1139522
pubmed: 17872438
Lafaille FG, Pessach IM, Zhang SY, Ciancanelli MJ, Herman M, Abhyankar A, et al. Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells. Nature. 2012;491:769–73. https://doi.org/10.1038/nature11583 .
doi: 10.1038/nature11583
pubmed: 23103873
pmcid: 3527075
Andersen LL, Mørk N, Reinert LS, Kofod-Olsen E, Narita R, Jørgensen SE, et al. Functional IRF3 deficiency in a patient with herpes simplex encephalitis. J Exp Med. 2015;212:1371–9. https://doi.org/10.1084/jem.20142274 .
doi: 10.1084/jem.20142274
pubmed: 26216125
pmcid: 4548062
Herman M, Ciancanelli M, Ou YH, Lorenzo L, Klaudel-Dreszler M, Pauwels E, et al. Heterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex encephalitis of childhood. J Exp Med. 2012;209:1567–82. https://doi.org/10.1084/jem.20111316 .
doi: 10.1084/jem.20111316
pubmed: 22851595
pmcid: 3428952
Pérez de Diego R, Sancho-Shimizu V, Lorenzo L, Puel A, Plancoulaine S, Picard C, et al. Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis. Immunity. 2010;33:400–11. https://doi.org/10.1016/j.immuni.2010.08.014 .
doi: 10.1016/j.immuni.2010.08.014
pubmed: 20832341
Sancho-Shimizu V, Pérez de Diego R, Lorenzo L, Halwani R, Alangari A, Israelsson E, et al. Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency. J Clin Investig. 2011;121:4889–902. https://doi.org/10.1172/JCI59259 .
doi: 10.1172/JCI59259
pubmed: 22105173
pmcid: 3226004
Tucker MH, Yu W, Menden H, Xia S, Schreck CF, Gibson M, et al. IRF7 and UNC93B1 variants in an infant with recurrent herpes simplex virus infection. J Clin Investig. 2023;133:e154016. https://doi.org/10.1172/JCI154016 .
doi: 10.1172/JCI154016
pubmed: 37097753
pmcid: 10231989
Chen J, Jing H, Martin-Nalda A, Bastard P, Rivière JG, Liu Z, et al. Inborn errors of TLR3- or MDA5-dependent type I IFN immunity in children with enterovirus rhombencephalitis. J Exp Med. 2021;218:e20211349. https://doi.org/10.1084/jem.20211349 .
doi: 10.1084/jem.20211349
pubmed: 34726731
pmcid: 8570298
Sironi M, Peri AM, Cagliani R, Forni D, Riva S, Biasin M, et al. TLR3 mutations in adult patients with Herpes Simplex Virus and Varicella-Zoster Virus Encephalitis. J Infect Dis. 2017;215:1430–4. https://doi.org/10.1093/infdis/jix166 .
doi: 10.1093/infdis/jix166
pubmed: 28368532
Hidaka F, Matsuo S, Muta T, Takeshige K, Mizukami T, Nunoi H. A missense mutation of the Toll-like receptor 3 gene in a patient with influenza-associated encephalopathy. Clin Immunol. 2006;119:188–94. https://doi.org/10.1016/j.clim.2006.01.005 .
doi: 10.1016/j.clim.2006.01.005
pubmed: 16517210
Kindberg E, Vene S, Mickiene A, Lundkvist Å, Lindquist L, Svensson L. A functional Toll-like receptor 3 gene (TLR3) may be a risk factor for tick-borne encephalitis virus (TBEV) infection. J Infect Dis. 2011;203:523–8. https://doi.org/10.1093/infdis/jiq082 .
doi: 10.1093/infdis/jiq082
pubmed: 21216866
pmcid: 3071239
Guo Q, Jin Y, Chen X, Ye X, Shen X, Lin M, et al. NF-kappaB in biology and targeted therapy: new insights and translational implications. Signal Transduct Target Ther. 2024;9:53. https://doi.org/10.1038/s41392-024-01757-9 .
doi: 10.1038/s41392-024-01757-9
pubmed: 38433280
pmcid: 10910037
Niehues T, Reichenbach J, Neubert J, Gudowius S, Puel A, Horneff G, et al. Nuclear factor kappaB essential modulator-deficient child with immunodeficiency yet without anhidrotic ectodermal dysplasia. J Allergy Clin Immunol. 2004;114:1456–62. https://doi.org/10.1016/j.jaci.2004.08.047 .
doi: 10.1016/j.jaci.2004.08.047
pubmed: 15577852
Audry M, Ciancanelli M, Yang K, Cobat A, Chang HH, Sancho-Shimizu V, et al. NEMO is a key component of NF-kappaB- and IRF-3-dependent TLR3-mediated immunity to herpes simplex virus. J Allergy Clin Immunol. 2011;128:610–7.e611-614. https://doi.org/10.1016/j.jaci.2011.04.059 .
doi: 10.1016/j.jaci.2011.04.059
pubmed: 21722947
pmcid: 3164951
Chiu YH, Macmillan JB, Chen ZJ. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell. 2009;138:576–91. https://doi.org/10.1016/j.cell.2009.06.015 .
doi: 10.1016/j.cell.2009.06.015
pubmed: 19631370
pmcid: 2747301
Ogunjimi B, Zhang SY, Sørensen KB, Skipper KA, Carter-Timofte M, Kerner G, et al. Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections. J Clin Investig. 2017;127:3543–56. https://doi.org/10.1172/JCI92280 .
doi: 10.1172/JCI92280
pubmed: 28783042
pmcid: 5669568
Bibert S, Piret J, Quinodoz M, Collinet E, Zoete V, Michielin O, et al. Herpes simplex encephalitis in adult patients with MASP-2 deficiency. PLoS Pathog. 2019;15:e1008168. https://doi.org/10.1371/journal.ppat.1008168 .
doi: 10.1371/journal.ppat.1008168
pubmed: 31869396
pmcid: 6944389
Errett JS, Suthar MS, McMillan A, Diamond MS, Gale M Jr. The essential, nonredundant roles of RIG-I and MDA5 in detecting and controlling West Nile virus infection. J Virol. 2013;87:11416–25. https://doi.org/10.1128/JVI.01488-13 .
doi: 10.1128/JVI.01488-13
pubmed: 23966395
pmcid: 3807316
Zhao J, Vijay R, Zhao J, Gale M Jr, Diamond MS, Perlman S. MAVS expressed by hematopoietic cells is critical for control of west nile virus infection and pathogenesis. J Virol. 2016;90:7098–108. https://doi.org/10.1128/JVI.00707-16 .
doi: 10.1128/JVI.00707-16
pubmed: 27226371
pmcid: 4984631
Hum NR, Bourguet FA, Sebastian A, Lam D, Phillips AM, Sanchez KR, et al. MAVS mediates a protective immune response in the brain to Rift Valley fever virus. PLoS Pathog. 2022;18:e1010231. https://doi.org/10.1371/journal.ppat.1010231 .
doi: 10.1371/journal.ppat.1010231
pubmed: 35584192
pmcid: 9154093
Zhou D, Li Q, Jia F, Zhang L, Wan S, Li Y, et al. The Japanese Encephalitis virus NS1’ protein inhibits type I IFN production by targeting MAVS. J Immunol. 2020;204:1287–98. https://doi.org/10.4049/jimmunol.1900946 .
doi: 10.4049/jimmunol.1900946
pubmed: 31996459
Ablasser A, Bauernfeind F, Hartmann G, Latz E, Fitzgerald KA, Hornung V. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat Immunol. 2009;10:1065–72. https://doi.org/10.1038/ni.1779 .
doi: 10.1038/ni.1779
pubmed: 19609254
Chiang JJ, Sparrer K, van Gent M, Lässig C, Huang T, Osterrieder N, et al. Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity. Nat Immunol. 2018;19:53–62. https://doi.org/10.1038/s41590-017-0005-y .
doi: 10.1038/s41590-017-0005-y
pubmed: 29180807
Naesens L, Muppala S, Acharya D, Nemegeer J, Bogaert D, Lee JH, et al. GTF3A mutations predispose to herpes simplex encephalitis by disrupting biogenesis of the host-derived RIG-I ligand RNA5SP141. Sci Immunol. 2022;7:eabq4531. https://doi.org/10.1126/sciimmunol.abq4531 .
doi: 10.1126/sciimmunol.abq4531
pubmed: 36399538
pmcid: 10075094
Ciganda M, Williams N. Eukaryotic 5S rRNA biogenesis. Wiley Interdiscip Rev RNA. 2011;2:523–33. https://doi.org/10.1002/wrna.74 .
doi: 10.1002/wrna.74
pubmed: 21957041
pmcid: 3278907
Borish L, Ayars AG, Kirkpatrick CH. Common variable immunodeficiency presenting as herpes simplex virus encephalitis. J Allergy Clin Immunol. 2011;127:541–3. https://doi.org/10.1016/j.jaci.2010.11.004 .
doi: 10.1016/j.jaci.2010.11.004
pubmed: 21167568
Lafaille FG, Harschnitz O, Lee YS, Zhang P, Hasek ML, Kerner G, et al. Human SNORA31 variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis. Nat Med. 2019;25:1873–84. https://doi.org/10.1038/s41591-019-0672-3 .
doi: 10.1038/s41591-019-0672-3
pubmed: 31806906
pmcid: 7376819
Zhang SY, Clark NE, Freije CA, Pauwels E, Taggart AJ, Okada S, et al. Inborn errors of RNA lariat metabolism in humans with brainstem viral infection. Cell. 2018;172:952–65.e918. https://doi.org/10.1016/j.cell.2018.02.019 .
doi: 10.1016/j.cell.2018.02.019
pubmed: 29474921
pmcid: 5886375
DeBiasi RL, Kleinschmidt-DeMasters BK, Richardson-Burns S, Tyler KL. Central nervous system apoptosis in human herpes simplex virus and cytomegalovirus encephalitis. J Infect Dis. 2002;186:1547–57. https://doi.org/10.1086/345375 .
doi: 10.1086/345375
pubmed: 12447729
Liu Z, Garcia Reino EJ, Harschnitz O, Guo H, Chan YH, Khobrekar NV, et al. Encephalitis and poor neuronal death-mediated control of herpes simplex virus in human inherited RIPK3 deficiency. Sci Immunol. 2023;8:eade2860. https://doi.org/10.1126/sciimmunol.ade2860 .
doi: 10.1126/sciimmunol.ade2860
pubmed: 37083451
pmcid: 10337828
Hait AS, Olagnier D, Sancho-Shimizu V, Skipper KA, Helleberg M, Larsen SM, et al. Defects in LC3B2 and ATG4A underlie HSV2 meningitis and reveal a critical role for autophagy in antiviral defense in humans. Sci Immunol. 2020;5:eabc2691. https://doi.org/10.1126/sciimmunol.abc2691 .
doi: 10.1126/sciimmunol.abc2691
pubmed: 33310865
pmcid: 7611067
Kim J, Koo BK, Yoon KJ. Modeling host-virus interactions in viral infectious diseases using stem-cell-derived systems and CRISPR/Cas9 technology. Viruses. 2019;11:124. https://doi.org/10.3390/v11020124 .
doi: 10.3390/v11020124
pubmed: 30704043
pmcid: 6409779
Di Lullo E, Kriegstein AR. The use of brain organoids to investigate neural development and disease. Nat Rev Neurosci. 2017;18:573–84. https://doi.org/10.1038/nrn.2017.107 .
doi: 10.1038/nrn.2017.107
pubmed: 28878372
pmcid: 5667942
Duval K, Grover H, Han LH, Mou Y, Pegoraro AF, Fredberg J, Chen Z. Modeling physiological events in 2D vs. 3D cell culture. Physiology. 2017;32:266–77. https://doi.org/10.1152/physiol.00036.2016 .
doi: 10.1152/physiol.00036.2016
pubmed: 28615311
pmcid: 5545611
Samudyata, Oliveira AO, Malwade S, Rufino de Sousa N, Goparaju SK, Gracias J, et al. SARS-CoV-2 promotes microglial synapse elimination in human brain organoids. Mol Psychiatry. 2022;27:3939–50. https://doi.org/10.1038/s41380-022-01786-2 .
doi: 10.1038/s41380-022-01786-2
pubmed: 36198765
pmcid: 9533278
Cugola FR, Fernandes IR, Russo FB, Freitas BC, Dias JL, Guimarães KP, et al. The Brazilian Zika virus strain causes birth defects in experimental models. Nature. 2016;534:267–71. https://doi.org/10.1038/nature18296 .
doi: 10.1038/nature18296
pubmed: 27279226
pmcid: 4902174
Dang J, Tiwari SK, Lichinchi G, Qin Y, Patil VS, Eroshkin AM, Rana TM. Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3. Cell Stem Cell. 2016;19:258–65. https://doi.org/10.1016/j.stem.2016.04.014 .
doi: 10.1016/j.stem.2016.04.014
pubmed: 27162029
pmcid: 5116380
Krenn V, Bosone C, Burkard TR, Spanier J, Kalinke U, Calistri A, et al. Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly. Cell Stem Cell. 2021;28:1362–79. https://doi.org/10.1016/j.stem.2021.03.004 . e1367
doi: 10.1016/j.stem.2021.03.004
pubmed: 33838105
pmcid: 7611471
Xu R, Boreland AJ, Li X, Erickson C, Jin M, Atkins C, et al. Developing human pluripotent stem cell-based cerebral organoids with a controllable microglia ratio for modeling brain development and pathology. Stem Cell Rep. 2021;16:1923–37. https://doi.org/10.1016/j.stemcr.2021.06.011 .
doi: 10.1016/j.stemcr.2021.06.011
Sun G, Chiuppesi F, Chen X, Wang C, Tian E, Nguyen J, et al. Modeling human cytomegalovirus-induced microcephaly in human iPSC-derived brain organoids. Cell Rep. Med. 2020;1:100002. https://doi.org/10.1016/j.xcrm.2020.100002 .
doi: 10.1016/j.xcrm.2020.100002
pubmed: 33205055
pmcid: 7659592
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77:683–90. https://doi.org/10.1001/jamaneurol.2020.1127 .
doi: 10.1001/jamaneurol.2020.1127
pubmed: 32275288
Yi SA, Nam KH, Yun J, Gim D, Joe D, Kim YH, et al. Infection of brain organoids and 2D cortical neurons with SARS-CoV-2 pseudovirus. Viruses. 2020;12:1004. https://doi.org/10.3390/v12091004 .
doi: 10.3390/v12091004
pubmed: 32911874
pmcid: 7551632
Zhang BZ, Chu H, Han S, Shuai H, Deng J, Hu YF, et al. SARS-CoV-2 infects human neural progenitor cells and brain organoids. Cell Res. 2020;30:928–31. https://doi.org/10.1038/s41422-020-0390-x .
doi: 10.1038/s41422-020-0390-x
pubmed: 32753756
McMahon CL, Staples H, Gazi M, Carrion R, Hsieh J. SARS-CoV-2 targets glial cells in human cortical organoids. Stem Cell Rep. 2021;16:1156–64. https://doi.org/10.1016/j.stemcr.2021.01.016 .
doi: 10.1016/j.stemcr.2021.01.016
Jacob F, Pather SR, Huang WK, Zhang F, Wong S, Zhou H, et al. Human pluripotent stem cell-derived neural cells and brain organoids reveal SARS-CoV-2 neurotropism predominates in choroid plexus epithelium. Cell Stem Cell. 2020;27:937–50. https://doi.org/10.1016/j.stem.2020.09.016 . e939
doi: 10.1016/j.stem.2020.09.016
pubmed: 33010822
pmcid: 7505550
Hou Y, Li C, Yoon C, Leung OW, You S, Cui X, et al. Enhanced replication of SARS-CoV-2 Omicron BA.2 in human forebrain and midbrain organoids. Signal Transduct Target Ther. 2022;7:381. https://doi.org/10.1038/s41392-022-01241-2 .
doi: 10.1038/s41392-022-01241-2
pubmed: 36411276
pmcid: 9676899
Rio-Hortega D. El tercer elemento de los centros nerviosos. I. La microglia en estado normal. II. Intervencion de la microglia en los procesos patologicos. III. Naturaleza probable de la microglia. Bol de la Soc esp de Biol. 1919;9:69.
Waltl I, Kalinke U. Beneficial and detrimental functions of microglia during viral encephalitis. Trends Neurosci. 2022;45:158–70. https://doi.org/10.1016/j.tins.2021.11.004 .
doi: 10.1016/j.tins.2021.11.004
pubmed: 34906391
Wang Y, Szretter KJ, Vermi W, Gilfillan S, Rossini C, Cella M, et al. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat Immunol. 2012;13:753–60. https://doi.org/10.1038/ni.2360 .
doi: 10.1038/ni.2360
pubmed: 22729249
pmcid: 3941469
Wheeler DL, Sariol A, Meyerholz DK, Perlman S. Microglia are required for protection against lethal coronavirus encephalitis in mice. J Clin Investig. 2018;128:931–43. https://doi.org/10.1172/JCI97229 .
doi: 10.1172/JCI97229
pubmed: 29376888
pmcid: 5824854
Tsai TT, Chen CL, Lin YS, Chang CP, Tsai CC, Cheng YL, et al. Microglia retard dengue virus-induced acute viral encephalitis. Sci Rep. 2016;6:27670. https://doi.org/10.1038/srep27670 .
doi: 10.1038/srep27670
pubmed: 27279150
pmcid: 4899773
Seitz S, Clarke P, Tyler KL. Pharmacologic depletion of microglia increases viral load in the brain and enhances mortality in murine models of flavivirus-induced encephalitis. J Virol. 2018;92:e00525–18. https://doi.org/10.1128/JVI.00525-18 .
doi: 10.1128/JVI.00525-18
pubmed: 29899084
pmcid: 6069207
Fekete R, Cserép C, Lénárt N, Tóth K, Orsolits B, Martinecz B, et al. Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms. Acta Neuropathol. 2018;136:461–82. https://doi.org/10.1007/s00401-018-1885-0 .
doi: 10.1007/s00401-018-1885-0
pubmed: 30027450
pmcid: 6096730
Waltl I, Käufer C, Gerhauser I, Chhatbar C, Ghita L, Kalinke U, Löscher W. Microglia have a protective role in viral encephalitis-induced seizure development and hippocampal damage. Brain Behav Immun. 2018;74:186–204. https://doi.org/10.1016/j.bbi.2018.09.006 .
doi: 10.1016/j.bbi.2018.09.006
pubmed: 30217535
pmcid: 7111316
Gern OL, Mulenge F, Pavlou A, Ghita L, Steffen I, Stangel M, Kalinke U. Toll-like receptors in viral encephalitis. Viruses. 2021;13:2065. https://doi.org/10.3390/v13102065 .
doi: 10.3390/v13102065
pubmed: 34696494
pmcid: 8540543
Crill EK, Furr-Rogers SR, Marriott I. RIG-I is required for VSV-induced cytokine production by murine glia and acts in combination with DAI to initiate responses to HSV-1. Glia. 2015;63:2168–80. https://doi.org/10.1002/glia.22883 .
doi: 10.1002/glia.22883
pubmed: 26146945
pmcid: 4600648
Liu B, Wang K, Gao HM, Mandavilli B, Wang JY, Hong JS. Molecular consequences of activated microglia in the brain: overactivation induces apoptosis. J Neurochem. 2001;77:182–9. https://doi.org/10.1046/j.1471-4159.2001.t01-1-00216.x .
doi: 10.1046/j.1471-4159.2001.t01-1-00216.x
pubmed: 11279274
Town T, Jeng D, Alexopoulou L, Tan J, Flavell RA. Microglia recognize double-stranded RNA via TLR3. J Immunol. 2006;176:3804–12. https://doi.org/10.4049/jimmunol.176.6.3804 .
doi: 10.4049/jimmunol.176.6.3804
pubmed: 16517751
Reinert LS, Rashidi AS, Tran DN, Katzilieris-Petras G, Hvidt AK, Gohr M, et al. Brain immune cells undergo cGAS/STING-dependent apoptosis during herpes simplex virus type 1 infection to limit type I IFN production. J Clin Investig. 2021;131:e136824. https://doi.org/10.1172/JCI136824 .
doi: 10.1172/JCI136824
pubmed: 32990676
pmcid: 7773356
Katzilieris-Petras G, Lai X, Rashidi AS, Verjans G, Reinert LS, Paludan SR. Microglia activate early antiviral responses upon herpes simplex virus 1 entry into the brain to counteract development of encephalitis-like disease in mice. J Virol. 2022;96:e0131121. https://doi.org/10.1128/JVI.01311-21 .
doi: 10.1128/JVI.01311-21
pubmed: 35045263
Reinert LS, Lopušná K, Winther H, Sun C, Thomsen MK, Nandakumar R, et al. Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS. Nat Commun. 2016;7:13348. https://doi.org/10.1038/ncomms13348 .
doi: 10.1038/ncomms13348
pubmed: 27830700
pmcid: 5109551
Käufer C, Chhatbar C, Bröer S, Waltl I, Ghita L, Gerhauser I, et al. Chemokine receptors CCR2 and CX3CR1 regulate viral encephalitis-induced hippocampal damage but not seizures. Proc Natl Acad Sci USA. 2018;115:E8929–E8938. https://doi.org/10.1073/pnas.1806754115 .
doi: 10.1073/pnas.1806754115
pubmed: 30181265
pmcid: 6156634
Zhang C, Yan Y, He H, Wang L, Zhang N, Zhang J, et al. IFN-stimulated P2Y13 protects mice from viral infection by suppressing the cAMP/EPAC1 signaling pathway. J Mol Cell Biol. 2019;11:395–407. https://doi.org/10.1093/jmcb/mjy045 .
doi: 10.1093/jmcb/mjy045
pubmed: 30137373
Yamashiro LH, Wilson SC, Morrison HM, Karalis V, Chung JJ, Chen KJ, et al. Interferon-independent STING signaling promotes resistance to HSV-1 in vivo. Nat Commun. 2020;11:3382. https://doi.org/10.1038/s41467-020-17156-x .
doi: 10.1038/s41467-020-17156-x
pubmed: 32636381
pmcid: 7341812
Enlow W, Bordeleau M, Piret J, Ibáñez FG, Uyar O, Venable MC, et al. Microglia are involved in phagocytosis and extracellular digestion during Zika virus encephalitis in young adult immunodeficient mice. J Neuroinflamm 2021;18:178. https://doi.org/10.1186/s12974-021-02221-z .
doi: 10.1186/s12974-021-02221-z
Jeong GU, Lyu J, Kim KD, Chung YC, Yoon GY, Lee S, et al. SARS-CoV-2 infection of microglia elicits proinflammatory activation and apoptotic cell death. Microbiol Spectr. 2022;10:e0109122. https://doi.org/10.1128/spectrum.01091-22 .
doi: 10.1128/spectrum.01091-22
pubmed: 35510852
Levtova N, Healy LM, Gonczi C, Stopnicki B, Blain M, Kennedy TE, et al. Comparative morphology and phagocytic capacity of primary human adult microglia with time-lapse imaging. J Neuroimmunol. 2017;310:143–9. https://doi.org/10.1016/j.jneuroim.2017.05.012 .
doi: 10.1016/j.jneuroim.2017.05.012
pubmed: 28606377
Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 2005;308:1314–8. https://doi.org/10.1126/science.1110647 .
doi: 10.1126/science.1110647
pubmed: 15831717
abd-el-Basset E, Fedoroff S. Effect of bacterial wall lipopolysaccharide (LPS) on morphology, motility, and cytoskeletal organization of microglia in cultures. J Neurosci Res. 1995;41:222–37. https://doi.org/10.1002/jnr.490410210 .
doi: 10.1002/jnr.490410210
pubmed: 7650758
Boje KM, Arora PK. Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death. Brain Res. 1992;587:250–6. https://doi.org/10.1016/0006-8993(92)91004-x .
doi: 10.1016/0006-8993(92)91004-x
pubmed: 1381982
Jurado KA, Yockey LJ, Wong PW, Lee S, Huttner AJ, Iwasaki A. Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice. Nat Microbiol. 2018;3:141–7. https://doi.org/10.1038/s41564-017-0060-z .
doi: 10.1038/s41564-017-0060-z
pubmed: 29158604
Garber C, Soung A, Vollmer LL, Kanmogne M, Last A, Brown J, Klein RS. T cells promote microglia-mediated synaptic elimination and cognitive dysfunction during recovery from neuropathogenic flaviviruses. Nat Neurosci. 2019;22:1276–88. https://doi.org/10.1038/s41593-019-0427-y .
doi: 10.1038/s41593-019-0427-y
pubmed: 31235930
pmcid: 6822175
Vasek MJ, Garber C, Dorsey D, Durrant DM, Bollman B, Soung A, et al. A complement-microglial axis drives synapse loss during virus-induced memory impairment. Nature. 2016;534:538–43. https://doi.org/10.1038/nature18283 .
doi: 10.1038/nature18283
pubmed: 27337340
pmcid: 5452615
Di Liberto G, Pantelyushin S, Kreutzfeldt M, Page N, Musardo S, Coras R, et al. Neurons under T cell attack coordinate phagocyte-mediated synaptic stripping. Cell. 2018;175:458–71. https://doi.org/10.1016/j.cell.2018.07.049 . e419
doi: 10.1016/j.cell.2018.07.049
pubmed: 30173917
Karrer U, Althage A, Odermatt B, Roberts CW, Korsmeyer SJ, Miyawaki S, et al. On the key role of secondary lymphoid organs in antiviral immune responses studied in alymphoplastic (aly/aly) and spleenless (Hox11(-)/-) mutant mice. J Exp Med. 1997;185:2157–70. https://doi.org/10.1084/jem.185.12.2157 .
doi: 10.1084/jem.185.12.2157
pubmed: 9182687
pmcid: 2196355
Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523:337–41. https://doi.org/10.1038/nature14432 .
doi: 10.1038/nature14432
pubmed: 26030524
pmcid: 4506234
Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M, et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. 2015;212:991–9. https://doi.org/10.1084/jem.20142290 .
doi: 10.1084/jem.20142290
pubmed: 26077718
pmcid: 4493418
Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, et al. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018;21:1380–91. https://doi.org/10.1038/s41593-018-0227-9 .
doi: 10.1038/s41593-018-0227-9
pubmed: 30224810
pmcid: 6214619
Hsu M, Rayasam A, Kijak JA, Choi YH, Harding JS, Marcus SA, et al. Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells. Nat Commun. 2019;10:229. https://doi.org/10.1038/s41467-018-08163-0 .
doi: 10.1038/s41467-018-08163-0
pubmed: 30651548
pmcid: 6335416
Li X, Qi L, Yang D, Hao S, Zhang F, Zhu X, et al. Meningeal lymphatic vessels mediate neurotropic viral drainage from the central nervous system. Nat Neurosci. 2022;25:577–87. https://doi.org/10.1038/s41593-022-01063-z .
doi: 10.1038/s41593-022-01063-z
pubmed: 35524140
Hickman HD, Takeda K, Skon CN, Murray FR, Hensley SE, Loomis J, et al. Direct priming of antiviral CD8+ T cells in the peripheral interfollicular region of lymph nodes. Nat Immunol. 2008;9:155–65. https://doi.org/10.1038/ni1557 .
doi: 10.1038/ni1557
pubmed: 18193049
Wang Y, Lobigs M, Lee E, Mullbacher A. CD8+ T cells mediate recovery and immunopathology in West Nile virus encephalitis. J Virol. 2003;77:13323–34. https://doi.org/10.1128/jvi.77.24.13323-13334.2003 .
doi: 10.1128/jvi.77.24.13323-13334.2003
pubmed: 14645588
pmcid: 296062
Anglen CS, Truckenmiller ME, Schell TD, Bonneau RH. The dual role of CD8+ T lymphocytes in the development of stress-induced herpes simplex encephalitis. J Neuroimmunol. 2003;140:13–27. https://doi.org/10.1016/s0165-5728(03)00159-0 .
doi: 10.1016/s0165-5728(03)00159-0
pubmed: 12864968
Shrestha B, Diamond MS. Role of CD8+ T cells in control of West Nile virus infection. J Virol. 2004;78:8312–21. https://doi.org/10.1128/JVI.78.15.8312-8321.2004 .
doi: 10.1128/JVI.78.15.8312-8321.2004
pubmed: 15254203
pmcid: 446114
Růzek D, Salát J, Palus M, Gritsun TS, Gould EA, Dyková I, et al. CD8+ T-cells mediate immunopathology in tick-borne encephalitis. Virology. 2009;384:1–6. https://doi.org/10.1016/j.virol.2008.11.023 .
doi: 10.1016/j.virol.2008.11.023
pubmed: 19070884
Jain N, Oswal N, Chawla AS, Agrawal T, Biswas M, Vrati S, et al. CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function. PLoS Negl Trop Dis. 2017;11:e0005329. https://doi.org/10.1371/journal.pntd.0005329 .
doi: 10.1371/journal.pntd.0005329
pubmed: 28151989
pmcid: 5308832
Koyanagi N, Imai T, Shindo K, Sato A, Fujii W, Ichinohe T, et al. Herpes simplex virus-1 evasion of CD8+ T cell accumulation contributes to viral encephalitis. J Clin Investig. 2017;127:3784–95. https://doi.org/10.1172/JCI92931 .
doi: 10.1172/JCI92931
pubmed: 28891812
pmcid: 5617679
Rall GF, Manchester M, Daniels LR, Callahan EM, Belman AR, Oldstone MB. A transgenic mouse model for measles virus infection of the brain. Proc Natl Acad Sci USA. 1997;94:4659–63. https://doi.org/10.1073/pnas.94.9.4659 .
doi: 10.1073/pnas.94.9.4659
pubmed: 9114047
pmcid: 20780
Patterson CE, Daley JK, Echols LA, Lane TE, Rall GF. Measles virus infection induces chemokine synthesis by neurons. J Immunol. 2003;171:3102–9. https://doi.org/10.4049/jimmunol.171.6.3102 .
doi: 10.4049/jimmunol.171.6.3102
pubmed: 12960336
Klein RS, Lin E, Zhang B, Luster AD, Tollett J, Samuel MA, et al. Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis. J Virol. 2005;79:11457–66. https://doi.org/10.1128/JVI.79.17.11457-11466.2005 .
doi: 10.1128/JVI.79.17.11457-11466.2005
pubmed: 16103196
pmcid: 1193600
Wuest TR, Carr DJ. Dysregulation of CXCR3 signaling due to CXCL10 deficiency impairs the antiviral response to herpes simplex virus 1 infection. J Immunol. 2008;181:7985–93. https://doi.org/10.4049/jimmunol.181.11.7985 .
doi: 10.4049/jimmunol.181.11.7985
pubmed: 19017990
Zhang B, Chan YK, Lu B, Diamond MS, Klein RS. CXCR3 mediates region-specific antiviral T cell trafficking within the central nervous system during West Nile virus encephalitis. J Immunol. 2008;180:2641–9. https://doi.org/10.4049/jimmunol.180.4.2641 .
doi: 10.4049/jimmunol.180.4.2641
pubmed: 18250476
Lang KS, Navarini AA, Recher M, Lang PA, Heikenwalder M, Stecher B, et al. MyD88 protects from lethal encephalitis during infection with vesicular stomatitis virus. Eur J Immunol. 2007;37:2434–40. https://doi.org/10.1002/eji.200737310 .
doi: 10.1002/eji.200737310
pubmed: 17668900
Szretter KJ, Daffis S, Patel J, Suthar MS, Klein RS, Gale M Jr, Diamond MS. The innate immune adaptor molecule MyD88 restricts West Nile virus replication and spread in neurons of the central nervous system. J Virol. 2010;84:12125–38. https://doi.org/10.1128/JVI.01026-10 .
doi: 10.1128/JVI.01026-10
pubmed: 20881045
pmcid: 2976388
Christensen JE, de Lemos C, Moos T, Christensen JP, Thomsen AR. CXCL10 is the key ligand for CXCR3 on CD8+ effector T cells involved in immune surveillance of the lymphocytic choriomeningitis virus-infected central nervous system. J Immunol. 2006;176:4235–43. https://doi.org/10.4049/jimmunol.176.7.4235 .
doi: 10.4049/jimmunol.176.7.4235
pubmed: 16547260
Christensen JE, Simonsen S, Fenger C, Sørensen MR, Moos T, Christensen JP, et al. Fulminant lymphocytic choriomeningitis virus-induced inflammation of the CNS involves a cytokine-chemokine-cytokine-chemokine cascade. J Immunol. 2009;182:1079–87. https://doi.org/10.4049/jimmunol.182.2.1079 .
doi: 10.4049/jimmunol.182.2.1079
pubmed: 19124751
Glass WG, Lim JK, Cholera R, Pletnev AG, Gao JL, Murphy PM. Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection. J Exp Med. 2005;202:1087–98. https://doi.org/10.1084/jem.20042530 .
doi: 10.1084/jem.20042530
pubmed: 16230476
pmcid: 2213214
Michlmayr D, Bardina SV, Rodriguez CA, Pletnev AG, Lim JK. Dual function of Ccr5 during langat virus encephalitis: reduction in neutrophil-mediated central nervous system inflammation and increase in T cell-mediated viral clearance. J Immunol. 2016;196:4622–31. https://doi.org/10.4049/jimmunol.1502452 .
doi: 10.4049/jimmunol.1502452
pubmed: 27183602
Larena M, Regner M, Lobigs M. The chemokine receptor CCR5, a therapeutic target for HIV/AIDS antagonists, is critical for recovery in a mouse model of Japanese encephalitis. PLoS One. 2012;7:e44834. https://doi.org/10.1371/journal.pone.0044834 .
doi: 10.1371/journal.pone.0044834
pubmed: 23028638
pmcid: 3448613
Cupovic J, Onder L, Gil-Cruz C, Weiler E, Caviezel-Firner S, Perez-Shibayama C, et al. Central nervous system stromal cells control local CD8(+) T cell responses during virus-induced neuroinflammation. Immunity. 2016;44:622–33. https://doi.org/10.1016/j.immuni.2015.12.022 .
doi: 10.1016/j.immuni.2015.12.022
pubmed: 26921107
pmcid: 7111064
McCandless EE, Zhang B, Diamond MS, Klein RS. CXCR4 antagonism increases T cell trafficking in the central nervous system and improves survival from West Nile virus encephalitis. Proc Natl Acad Sci USA. 2008;105:11270–5. https://doi.org/10.1073/pnas.0800898105 .
doi: 10.1073/pnas.0800898105
pubmed: 18678898
pmcid: 2495012
Durrant DM, Daniels BP, Klein RS. IL-1R1 signaling regulates CXCL12-mediated T cell localization and fate within the central nervous system during West Nile Virus encephalitis. J Immunol. 2014;193:4095–106. https://doi.org/10.4049/jimmunol.1401192 .
doi: 10.4049/jimmunol.1401192
pubmed: 25200953
Herz J, Johnson KR, McGavern DB. Therapeutic antiviral T cells noncytopathically clear persistently infected microglia after conversion into antigen-presenting cells. J Exp Med. 2015;212:1153–69. https://doi.org/10.1084/jem.20142047 .
doi: 10.1084/jem.20142047
pubmed: 26122661
pmcid: 4516789
Funk KE, Klein RS. CSF1R antagonism limits local restimulation of antiviral CD8(+) T cells during viral encephalitis. J Neuroinflamm. 2019;16:22. https://doi.org/10.1186/s12974-019-1397-4 .
doi: 10.1186/s12974-019-1397-4
Brizić I, Hiršl L, Šustić M, Golemac M, Britt WJ, Krmpotić A, Jonjić S. CD4 T cells are required for maintenance of CD8 T(RM) cells and virus control in the brain of MCMV-infected newborn mice. Med Microbiol Immunol. 2019;208:487–94. https://doi.org/10.1007/s00430-019-00601-0 .
doi: 10.1007/s00430-019-00601-0
pubmed: 30923899
pmcid: 6640853
Phares TW, Stohlman SA, Hwang M, Min B, Hinton DR, Bergmann CC. CD4 T cells promote CD8 T cell immunity at the priming and effector site during viral encephalitis. J Virol. 2012;86:2416–27. https://doi.org/10.1128/JVI.06797-11 .
doi: 10.1128/JVI.06797-11
pubmed: 22205741
pmcid: 3302259
Ben-Nathan D, Huitinga I, Lustig S, van Rooijen N, Kobiler D. West Nile virus neuroinvasion and encephalitis induced by macrophage depletion in mice. Arch Virol. 1996;141:459–69. https://doi.org/10.1007/BF01718310 .
doi: 10.1007/BF01718310
pubmed: 8645088
Purtha WE, Chachu KA, Virgin HWT, Diamond MS. Early B-cell activation after West Nile virus infection requires alpha/beta interferon but not antigen receptor signaling. J Virol. 2008;82:10964–74. https://doi.org/10.1128/JVI.01646-08 .
doi: 10.1128/JVI.01646-08
pubmed: 18786989
pmcid: 2573246
Tsou CL, Peters W, Si Y, Slaymaker S, Aslanian AM, Weisberg SP, et al. Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites. J Clin Invest. 2007;117:902–9. https://doi.org/10.1172/JCI29919 .
doi: 10.1172/JCI29919
pubmed: 17364026
pmcid: 1810572
Lim JK, Obara CJ, Rivollier A, Pletnev AG, Kelsall BL, Murphy PM. Chemokine receptor Ccr2 is critical for monocyte accumulation and survival in West Nile virus encephalitis. J Immunol. 2011;186:471–8. https://doi.org/10.4049/jimmunol.1003003 .
doi: 10.4049/jimmunol.1003003
pubmed: 21131425
Bardina SV, Michlmayr D, Hoffman KW, Obara CJ, Sum J, Charo IF, et al. Differential roles of chemokines CCL2 and CCL7 in monocytosis and leukocyte migration during West Nile virus infection. J Immunol. 2015;195:4306–18. https://doi.org/10.4049/jimmunol.1500352 .
doi: 10.4049/jimmunol.1500352
pubmed: 26401006
Howe CL, LaFrance-Corey RG, Goddery EN, Johnson RK, Mirchia K. Neuronal CCL2 expression drives inflammatory monocyte infiltration into the brain during acute virus infection. J Neuroinflamm. 2017;14:238. https://doi.org/10.1186/s12974-017-1015-2 .
doi: 10.1186/s12974-017-1015-2
Kim JH, Patil AM, Choi JY, Kim SB, Uyangaa E, Hossain FM, et al. CCL2, but not its receptor, is essential to restrict immune privileged central nervous system-invasion of Japanese encephalitis virus via regulating accumulation of CD11b(+) Ly-6C(hi) monocytes. Immunology. 2016;149:186–203. https://doi.org/10.1111/imm.12626 .
doi: 10.1111/imm.12626
pubmed: 27260136
pmcid: 5011677
Trujillo JA, Fleming EL, Perlman S. Transgenic CCL2 expression in the central nervous system results in a dysregulated immune response and enhanced lethality after coronavirus infection. J Virol. 2013;87:2376–89. https://doi.org/10.1128/JVI.03089-12 .
doi: 10.1128/JVI.03089-12
pubmed: 23269787
pmcid: 3571407
Kim JV, Kang SS, Dustin ML, McGavern DB. Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis. Nature. 2009;457:191–5. https://doi.org/10.1038/nature07591 .
doi: 10.1038/nature07591
pubmed: 19011611
Boivin N, Menasria R, Gosselin D, Rivest S, Boivin G. Impact of deficiency in CCR2 and CX3CR1 receptors on monocytes trafficking in herpes simplex virus encephalitis. J Gen Virol. 2012;93:1294–304. https://doi.org/10.1099/vir.0.041046-0 .
doi: 10.1099/vir.0.041046-0
pubmed: 22377584
Zhang N, Bevan MJ. CD8(+) T cells: foot soldiers of the immune system. Immunity. 2011;35:161–8. https://doi.org/10.1016/j.immuni.2011.07.010 .
doi: 10.1016/j.immuni.2011.07.010
pubmed: 21867926
pmcid: 3303224
Hausmann J, Pagenstecher A, Baur K, Richter K, Rziha HJ, Staeheli P. CD8 T cells require gamma interferon to clear borna disease virus from the brain and prevent immune system-mediated neuronal damage. J Virol. 2005;79:13509–18. https://doi.org/10.1128/JVI.79.21.13509-13518.2005 .
doi: 10.1128/JVI.79.21.13509-13518.2005
pubmed: 16227271
pmcid: 1262614
Osinska I, Popko K, Demkow U. Perforin: an important player in immune response. Cent Eur J Immunol. 2014;39:109–15. https://doi.org/10.5114/ceji.2014.42135 .
doi: 10.5114/ceji.2014.42135
pubmed: 26155110
pmcid: 4439970
Shrestha B, Diamond MS. Fas ligand interactions contribute to CD8+ T-cell-mediated control of West Nile virus infection in the central nervous system. J Virol. 2007;81:11749–57. https://doi.org/10.1128/JVI.01136-07 .
doi: 10.1128/JVI.01136-07
pubmed: 17804505
pmcid: 2168805
Shrestha B, Pinto AK, Green S, Bosch I, Diamond MS. CD8+ T cells use TRAIL to restrict West Nile virus pathogenesis by controlling infection in neurons. J Virol. 2012;86:8937–48. https://doi.org/10.1128/JVI.00673-12 .
doi: 10.1128/JVI.00673-12
pubmed: 22740407
pmcid: 3416144
Larena M, Regner M, Lee E, Lobigs M. Pivotal role of antibody and subsidiary contribution of CD8+ T cells to recovery from infection in a murine model of Japanese encephalitis. J Virol. 2011;85:5446–55. https://doi.org/10.1128/JVI.02611-10 .
doi: 10.1128/JVI.02611-10
pubmed: 21450826
pmcid: 3094953
Larena M, Regner M, Lobigs M. Cytolytic effector pathways and IFN-gamma help protect against Japanese encephalitis. Eur J Immunol. 2013;43:1789–98. https://doi.org/10.1002/eji.201243152 .
doi: 10.1002/eji.201243152
pubmed: 23568450
Binder GK, Griffin DE. Interferon-gamma-mediated site-specific clearance of alphavirus from CNS neurons. Science. 2001;293:303–6. https://doi.org/10.1126/science.1059742 .
doi: 10.1126/science.1059742
pubmed: 11452126
Wheeler DL, Athmer J, Meyerholz DK, Perlman S. Murine olfactory bulb interneurons survive infection with a neurotropic coronavirus. J Virol. 2017;91:e01099–17. https://doi.org/10.1128/JVI.01099-17 .
doi: 10.1128/JVI.01099-17
pubmed: 28835503
pmcid: 5660484
Knickelbein JE, Khanna KM, Yee MB, Baty CJ, Kinchington PR, Hendricks RL. Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency. Science. 2008;322:268–71. https://doi.org/10.1126/science.1164164 .
doi: 10.1126/science.1164164
pubmed: 18845757
pmcid: 2680315
Steinbach K, Vincenti I, Kreutzfeldt M, Page N, Muschaweckh A, Wagner I, et al. Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection. J Exp Med. 2016;213:1571–87. https://doi.org/10.1084/jem.20151916 .
doi: 10.1084/jem.20151916
pubmed: 27377586
pmcid: 4986533
Urban SL, Jensen IJ, Shan Q, Pewe LL, Xue HH, Badovinac VP, Harty JT. Peripherally induced brain tissue-resident memory CD8(+) T cells mediate protection against CNS infection. Nat Immunol. 2020;21:938–49. https://doi.org/10.1038/s41590-020-0711-8 .
doi: 10.1038/s41590-020-0711-8
pubmed: 32572242
pmcid: 7381383
Brizić I, Šušak B, Arapović M, Huszthy PC, Hiršl L, Kveštak D, et al. Brain-resident memory CD8(+) T cells induced by congenital CMV infection prevent brain pathology and virus reactivation. Eur J Immunol. 2018;48:950–64. https://doi.org/10.1002/eji.201847526 .
doi: 10.1002/eji.201847526
pubmed: 29500823
pmcid: 6422351
Smolders J, Heutinck KM, Fransen NL, Remmerswaal E, Hombrink P, Ten Berge I, et al. Tissue-resident memory T cells populate the human brain. Nat Commun. 2018;9:4593. https://doi.org/10.1038/s41467-018-07053-9 .
doi: 10.1038/s41467-018-07053-9
pubmed: 30389931
pmcid: 6214977
Rosen SF, Soung AL, Yang W, Ai S, Kanmogne M, Davé VA, et al. Single-cell RNA transcriptome analysis of CNS immune cells reveals CXCL16/CXCR6 as maintenance factors for tissue-resident T cells that drive synapse elimination. Genome Med. 2022;14:108. https://doi.org/10.1186/s13073-022-01111-0 .
doi: 10.1186/s13073-022-01111-0
pubmed: 36153630
pmcid: 9509564
VanGuilder HD, Vrana KE, Freeman WM. Twenty-five years of quantitative PCR for gene expression analysis. Biotechniques. 2008;44:619–26. https://doi.org/10.2144/000112776 .
doi: 10.2144/000112776
pubmed: 18474036
Schena M, Heller RA, Theriault TP, Konrad K, Lachenmeier E, Davis RW. Microarrays: biotechnology’s discovery platform for functional genomics. Trends Biotechnol. 1998;16:301–6. https://doi.org/10.1016/s0167-7799(98)01219-0 .
doi: 10.1016/s0167-7799(98)01219-0
pubmed: 9675914
Schena M, Shalon D, Davis RW, Brown PO. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science. 1995;270:467–70. https://doi.org/10.1126/science.270.5235.467 .
doi: 10.1126/science.270.5235.467
pubmed: 7569999
Geiss GK, Bumgarner RE, Birditt B, Dahl T, Dowidar N, Dunaway DL, et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol. 2008;26:317–25. https://doi.org/10.1038/nbt1385 .
doi: 10.1038/nbt1385
pubmed: 18278033
Nagalakshmi U, Wang Z, Waern K, Shou C, Raha D, Gerstein M, Snyder M. The transcriptional landscape of the yeast genome defined by RNA sequencing. Science. 2008;320:1344–9. https://doi.org/10.1126/science.1158441 .
doi: 10.1126/science.1158441
pubmed: 18451266
pmcid: 2951732
Hickman SE, Kingery ND, Ohsumi TK, Borowsky ML, Wang LC, Means TK, El Khoury J. The microglial sensome revealed by direct RNA sequencing. Nat Neurosci. 2013;16:1896–905. https://doi.org/10.1038/nn.3554 .
doi: 10.1038/nn.3554
pubmed: 24162652
pmcid: 3840123
Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, et al. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat Neurosci. 2014;17:131–43. https://doi.org/10.1038/nn.3599 .
doi: 10.1038/nn.3599
pubmed: 24316888
Gosselin D, Skola D, Coufal NG, Holtman IR, Schlachetzki J, Sajti E, et al. An environment-dependent transcriptional network specifies human microglia identity. Science. 2017;356:eaal3222. https://doi.org/10.1126/science.aal3222 .
doi: 10.1126/science.aal3222
pubmed: 28546318
pmcid: 5858585
Galatro TF, Holtman IR, Lerario AM, Vainchtein ID, Brouwer N, Sola PR, et al. Transcriptomic analysis of purified human cortical microglia reveals age-associated changes. Nat Neurosci. 2017;20:1162–71. https://doi.org/10.1038/nn.4597 .
doi: 10.1038/nn.4597
pubmed: 28671693
Sanz E, Yang L, Su T, Morris DR, McKnight GS, Amieux PS. Cell-type-specific isolation of ribosome-associated mRNA from complex tissues. Proc Natl Acad Sci USA. 2009;106:13939–44. https://doi.org/10.1073/pnas.0907143106 .
doi: 10.1073/pnas.0907143106
pubmed: 19666516
pmcid: 2728999
Haimon Z, Frumer GR, Kim JS, Trzebanski S, Haffner-Krausz R, Ben-Dor S, et al. Cognate microglia-T cell interactions shape the functional regulatory T cell pool in experimental autoimmune encephalomyelitis pathology. Nat Immunol. 2022;23:1749–62. https://doi.org/10.1038/s41590-022-01360-6 .
doi: 10.1038/s41590-022-01360-6
pubmed: 36456736
Acharjee S, Gordon P, Lee BH, Read J, Workentine ML, Sharkey KA, Pittman QJ. Characterization of microglial transcriptomes in the brain and spinal cord of mice in early and late experimental autoimmune encephalomyelitis using a RiboTag strategy. Sci Rep. 2021;11:14319. https://doi.org/10.1038/s41598-021-93590-1 .
doi: 10.1038/s41598-021-93590-1
pubmed: 34253764
pmcid: 8275680
Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, Ulland TK, et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell. 2017;169:1276–90.e1217. https://doi.org/10.1016/j.cell.2017.05.018 .
doi: 10.1016/j.cell.2017.05.018
pubmed: 28602351
Mathys H, Adaikkan C, Gao F, Young JZ, Manet E, Hemberg M, et al. Temporal tracking of microglia activation in neurodegeneration at single-cell resolution. Cell Rep. 2017;21:366–80. https://doi.org/10.1016/j.celrep.2017.09.039 .
doi: 10.1016/j.celrep.2017.09.039
pubmed: 29020624
pmcid: 5642107
Uyar O, Laflamme N, Piret J, Venable MC, Carbonneau J, Zarrouk K, et al. An early microglial response is needed to efficiently control herpes simplex virus encephalitis. J Virol. 2020;94:e01428–20. https://doi.org/10.1128/JVI.01428-20 .
doi: 10.1128/JVI.01428-20
pubmed: 32938766
pmcid: 7654270
Stephenson E, Reynolds G, Botting RA, Calero-Nieto FJ, Morgan MD, Tuong ZK, et al. Single-cell multi-omics analysis of the immune response in COVID-19. Nat Med. 2021;27:904–16. https://doi.org/10.1038/s41591-021-01329-2 .
doi: 10.1038/s41591-021-01329-2
pubmed: 33879890
pmcid: 8121667
Deczkowska A, Keren-Shaul H, Weiner A, Colonna M, Schwartz M, Amit I. Disease-associated microglia: a universal immune sensor of neurodegeneration. Cell. 2018;173:1073–81. https://doi.org/10.1016/j.cell.2018.05.003 .
doi: 10.1016/j.cell.2018.05.003
pubmed: 29775591
Ellwanger, DC, Wang S, Brioschi S, Shao Z, Green L, Case R, et al. Prior activation state shapes the microglia response to antihuman TREM2 in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA. 2021;18:e2017742118. https://doi.org/10.1073/pnas.2017742118 .
Syage AR, Ekiz HA, Skinner DD, Stone C, O’Connell RM, Lane TE. Single-cell RNA sequencing reveals the diversity of the immunological landscape following central nervous system infection by a murine coronavirus. J Virol. 2020;94:e01295–20. https://doi.org/10.1128/JVI.01295-20 .
doi: 10.1128/JVI.01295-20
pubmed: 32999036
pmcid: 7925182
Spiteri AG, Wishart CL, Ni D, Viengkhou B, Macia L, Hofer MJ, King N. Temporal tracking of microglial and monocyte single-cell transcriptomics in lethal flavivirus infection. Acta Neuropathol Commun. 2023;11:60. https://doi.org/10.1186/s40478-023-01547-4 .
doi: 10.1186/s40478-023-01547-4
pubmed: 37016414
pmcid: 10074823
Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol. 2003;3:133–46. https://doi.org/10.1038/nri1001 .
doi: 10.1038/nri1001
pubmed: 12563297
Li J, Gran B, Zhang GX, Ventura ES, Siglienti I, Rostami A, Kamoun M. Differential expression and regulation of IL-23 and IL-12 subunits and receptors in adult mouse microglia. J Neurol Sci. 2003;215:95–103. https://doi.org/10.1016/s0022-510x(03)00203-x .
doi: 10.1016/s0022-510x(03)00203-x
pubmed: 14568135
Pan J, Ma N, Yu B, Zhang W, Wan J. Transcriptomic profiling of microglia and astrocytes throughout aging. J Neuroinflamm. 2020;17:97. https://doi.org/10.1186/s12974-020-01774-9 .
doi: 10.1186/s12974-020-01774-9
Kreutzfeldt M, Bergthaler A, Fernandez M, Brück W, Steinbach K, Vorm M, et al. Neuroprotective intervention by interferon-gamma blockade prevents CD8+ T cell-mediated dendrite and synapse loss. J Exp Med. 2013;210:2087–103. https://doi.org/10.1084/jem.20122143 .
doi: 10.1084/jem.20122143
pubmed: 23999498
pmcid: 3782053
Maniatis S, Äijö T, Vickovic S, Braine C, Kang K, Mollbrink A, et al. Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis. Science. 2019;364:89–93. https://doi.org/10.1126/science.aav9776 .
doi: 10.1126/science.aav9776
pubmed: 30948552
Choi H, Lee EJ, Shin JS, Kim H, Bae S, Choi Y, Lee DS. Spatiotemporal characterization of glial cell activation in an Alzheimer’s disease model by spatially resolved transcriptomics. Exp Mol Med. 2023;55:2564–75. https://doi.org/10.1038/s12276-023-01123-9 .
doi: 10.1038/s12276-023-01123-9
pubmed: 38036733
pmcid: 10767047
Krasemann S, Madore C, Cialic R, Baufeld C, Calcagno N, El Fatimy R, et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity. 2017;47:566–81. https://doi.org/10.1016/j.immuni.2017.08.008 . e569
doi: 10.1016/j.immuni.2017.08.008
pubmed: 28930663
pmcid: 5719893
Sierksma A, Lu A, Mancuso R, Fattorelli N, Thrupp N, Salta E, et al. Novel Alzheimer risk genes determine the microglia response to amyloid-beta but not to TAU pathology. EMBO Mol Med. 2020;12:e10606. https://doi.org/10.15252/emmm.201910606 .
doi: 10.15252/emmm.201910606
pubmed: 31951107
pmcid: 7059012
Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M, et al. The antibody aducanumab reduces Abeta plaques in Alzheimer’s disease. Nature. 2016;537:50–56. https://doi.org/10.1038/nature19323 .
doi: 10.1038/nature19323
pubmed: 27582220
Long JM, Holtzman DM. Alzheimer disease: an update on pathobiology and treatment strategies. Cell. 2019;179:312–39. https://doi.org/10.1016/j.cell.2019.09.001 .
doi: 10.1016/j.cell.2019.09.001
pubmed: 31564456
pmcid: 6778042
Schneider L. A resurrection of aducanumab for Alzheimer’s disease. Lancet Neurol. 2020;19:111–2. https://doi.org/10.1016/S1474-4422(19)30480-6 .
doi: 10.1016/S1474-4422(19)30480-6
pubmed: 31978357
Chen WT, Lu A, Craessaerts K, Pavie B, Sala Frigerio C, Corthout N, et al. Spatial transcriptomics and in situ sequencing to study Alzheimer’s disease. Cell. 2020;182:976–91.e919. https://doi.org/10.1016/j.cell.2020.06.038 .
doi: 10.1016/j.cell.2020.06.038
pubmed: 32702314
Wood JI, Wong E, Joghee R, Balbaa A, Vitanova KS, Stringer KM, et al. Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology. Cell Rep. 2022;41:111686. https://doi.org/10.1016/j.celrep.2022.111686 .
doi: 10.1016/j.celrep.2022.111686
pubmed: 36417868
Gratuze M, Leyns CEG, Holtzman DM. New insights into the role of TREM2 in Alzheimer’s disease. Mol Neurodegener. 2018;13:66. https://doi.org/10.1186/s13024-018-0298-9 .
doi: 10.1186/s13024-018-0298-9
pubmed: 30572908
pmcid: 6302500
Kulkarni B, Kumar D, Cruz-Martins N, Sellamuthu S. Role of TREM2 in Alzheimer’s disease: a long road ahead. Mol Neurobiol. 2021;58:5239–52. https://doi.org/10.1007/s12035-021-02477-9 .
doi: 10.1007/s12035-021-02477-9
pubmed: 34275100
Liu W, Taso O, Wang R, Bayram S, Graham AC, Garcia-Reitboeck P, et al. Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions. Hum Mol Genet. 2020;29:3224–48. https://doi.org/10.1093/hmg/ddaa209 .
doi: 10.1093/hmg/ddaa209
pubmed: 32959884
pmcid: 7689298
Sankowski R, Böttcher C, Masuda T, Geirsdottir L, Sagar, Sindram E, et al. Mapping microglia states in the human brain through the integration of high-dimensional techniques. Nat Neurosci. 2019;22:2098–110. https://doi.org/10.1038/s41593-019-0532-y .
doi: 10.1038/s41593-019-0532-y
pubmed: 31740814
Masuda T, Sankowski R, Staszewski O, Böttcher C, Amann L, Sagar, et al. Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution. Nature. 2019;566:388–92. https://doi.org/10.1038/s41586-019-0924-x .
doi: 10.1038/s41586-019-0924-x
pubmed: 30760929
Vijayaragavan K, Cannon BJ, Tebaykin D, Bossé M, Baranski A, Oliveria JP, et al. Single-cell spatial proteomic imaging for human neuropathology. Acta Neuropathol Commun. 2022;10:158. https://doi.org/10.1186/s40478-022-01465-x .
doi: 10.1186/s40478-022-01465-x
pubmed: 36333818
pmcid: 9636771
Keren L, Bosse M, Thompson S, Risom T, Vijayaragavan K, McCaffrey E, et al. MIBI-TOF: a multiplexed imaging platform relates cellular phenotypes and tissue structure. Sci Adv. 2019;5:eaax5851. https://doi.org/10.1126/sciadv.aax5851 .
doi: 10.1126/sciadv.aax5851
pubmed: 31633026
pmcid: 6785247
Mrdjen, D, Liu CC, Greenwald NF, Kong A, McCaffrey EF, Leow KX, et al. Spatial proteomics reveals human microglial states shaped by anatomy and neuropathology. Res Sq. 2023. https://doi.org/10.21203/rs.3.rs-2987263/v1 .
Schwabenland M, Salié H, Tanevski J, Killmer S, Lago MS, Schlaak AE, et al. Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions. Immunity. 2021;54:1594–610.e1511. https://doi.org/10.1016/j.immuni.2021.06.002 .
doi: 10.1016/j.immuni.2021.06.002
pubmed: 34174183
pmcid: 8188302
Ooi MH, Lewthwaite P, Lai BF, Mohan A, Clear D, Lim L, et al. The epidemiology, clinical features, and long-term prognosis of Japanese encephalitis in central sarawak, malaysia, 1997-2005. Clin Infect Dis. 2008;47:458–68. https://doi.org/10.1086/590008 .
doi: 10.1086/590008
pubmed: 18616397
WHO. Japanese encephalitis, 2024 https://www.who.int/news-room/fact-sheets/detail/japanese-encephalitis .
Cusick MF, Libbey JE, Patel DC, Doty DJ, Fujinami RS. Infiltrating macrophages are key to the development of seizures following virus infection. J Virol. 2013;87:1849–60. https://doi.org/10.1128/JVI.02747-12 .
doi: 10.1128/JVI.02747-12
pubmed: 23236075
pmcid: 3554195
Vezzani A, Moneta D, Conti M, Richichi C, Ravizza T, De Luigi A, et al. Powerful anticonvulsant action of IL-1 receptor antagonist on intracerebral injection and astrocytic overexpression in mice. Proc Natl Acad Sci USA. 2000;97:11534–9. https://doi.org/10.1073/pnas.190206797 .
doi: 10.1073/pnas.190206797
pubmed: 11016948
pmcid: 17235
Zattoni M, Mura ML, Deprez F, Schwendener RA, Engelhardt B, Frei K, Fritschy JM. Brain infiltration of leukocytes contributes to the pathophysiology of temporal lobe epilepsy. J Neurosci. 2011;31:4037–50. https://doi.org/10.1523/JNEUROSCI.6210-10.2011 .
doi: 10.1523/JNEUROSCI.6210-10.2011
pubmed: 21411646
pmcid: 6623535
Libbey JE, Fujinami RS. Neurotropic viral infections leading to epilepsy: focus on Theiler’s murine encephalomyelitis virus. Future Virol. 2011;6:1339–50. https://doi.org/10.2217/fvl.11.107 .
doi: 10.2217/fvl.11.107
pubmed: 22267964
pmcid: 3259611
Bröer S, Käufer C, Haist V, Li L, Gerhauser I, Anjum M, et al. Brain inflammation, neurodegeneration and seizure development following picornavirus infection markedly differ among virus and mouse strains and substrains. Exp Neurol. 2016;279:57–74. https://doi.org/10.1016/j.expneurol.2016.02.011 .
doi: 10.1016/j.expneurol.2016.02.011
pubmed: 26892877
Waltl I, Käufer C, Bröer S, Chhatbar C, Ghita L, Gerhauser I, et al. Macrophage depletion by liposome-encapsulated clodronate suppresses seizures but not hippocampal damage after acute viral encephalitis. Neurobiol Dis. 2018;110:192–205. https://doi.org/10.1016/j.nbd.2017.12.001 .
doi: 10.1016/j.nbd.2017.12.001
pubmed: 29208406
DePaula-Silva AB, Hanak TJ, Libbey JE, Fujinami RS. Theiler’s murine encephalomyelitis virus infection of SJL/J and C57BL/6J mice: models for multiple sclerosis and epilepsy. J Neuroimmunol. 2017;308:30–42. https://doi.org/10.1016/j.jneuroim.2017.02.012 .
doi: 10.1016/j.jneuroim.2017.02.012
pubmed: 28237622
pmcid: 5474355
Zhang W, Chen Y, Pei H. C1q and central nervous system disorders. Front Immunol. 2023;14:1145649. https://doi.org/10.3389/fimmu.2023.1145649 .
doi: 10.3389/fimmu.2023.1145649
pubmed: 37033981
pmcid: 10076750
Wightman DP, Jansen IE, Savage JE, Shadrin AA, Bahrami S, Holland D, et al. A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease. Nat Genet. 2021;53:1276–82. https://doi.org/10.1038/s41588-021-00921-z .
doi: 10.1038/s41588-021-00921-z
pubmed: 34493870
pmcid: 10243600
Steel AJ, Eslick GD. Herpes viruses increase the risk of Alzheimer’s disease: a meta-analysis. J Alzheimers Dis. 2015;47:351–64. https://doi.org/10.3233/JAD-140822 .
doi: 10.3233/JAD-140822
pubmed: 26401558
Fruhwürth S, Reinert LS, Öberg C, Sakr M, Henricsson M, Zetterberg H, Paludan SR. TREM2 is down-regulated by HSV1 in microglia and involved in antiviral defense in the brain. Sci Adv. 2023;9:eadf5808. https://doi.org/10.1126/sciadv.adf5808 .
doi: 10.1126/sciadv.adf5808
pubmed: 37595041
pmcid: 10438464
Michael BD, Dunai C, Needham EJ, Tharmaratnam K, Williams R, Huang Y, et al. Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses. Nat Commun. 2023;14:8487. https://doi.org/10.1038/s41467-023-42320-4 .
doi: 10.1038/s41467-023-42320-4
pubmed: 38135686
pmcid: 10746705
Normandin E, Valizadeh N, Rudmann EA, Uddin R, Dobbins ST, MacInnis BL, et al. Neuropathological features of SARS-CoV-2 delta and omicron variants. J Neuropathol Exp Neurol. 2023;82:283–95. https://doi.org/10.1093/jnen/nlad015 .
doi: 10.1093/jnen/nlad015
pubmed: 36847705
pmcid: 10025880
Lucas C, Wong P, Klein J, Castro T, Silva J, Sundaram M, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature. 2020;584:463–9. https://doi.org/10.1038/s41586-020-2588-y .
doi: 10.1038/s41586-020-2588-y
pubmed: 32717743
pmcid: 7477538
Thwaites RS, Sanchez Sevilla Uruchurtu A, Siggins MK, Liew F, Russell CD, Moore SC, et al. Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. Sci Immunol. 2021;6:eabg9873. https://doi.org/10.1126/sciimmunol.abg9873 .
doi: 10.1126/sciimmunol.abg9873
pubmed: 33692097
pmcid: 8128298
Hosp JA, Dressing A, Blazhenets G, Bormann T, Rau A, Schwabenland M, et al. Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19. Brain. 2021;144:1263–76. https://doi.org/10.1093/brain/awab009 .
doi: 10.1093/brain/awab009
pubmed: 33822001
Morowitz JM, Pogson KB, Roque DA, Church FC. Role of SARS-CoV-2 in modifying neurodegenerative processes in Parkinson’s disease: a narrative review. Brain Sci. 2022;12:536. https://doi.org/10.3390/brainsci12050536 .
doi: 10.3390/brainsci12050536
pubmed: 35624923
pmcid: 9139310
Morris HR, Spillantini MG, Sue CM, Williams-Gray CH. The pathogenesis of Parkinson’s disease. Lancet. 2024;403:293–304. https://doi.org/10.1016/S0140-6736(23)01478-2 .
doi: 10.1016/S0140-6736(23)01478-2
pubmed: 38245249
Limphaibool N, Iwanowski P, Holstad MJV, Kobylarek D, Kozubski W. Infectious etiologies of Parkinsonism: pathomechanisms and clinical implications. Front Neurol. 2019;10:652. https://doi.org/10.3389/fneur.2019.00652 .
doi: 10.3389/fneur.2019.00652
pubmed: 31275235
pmcid: 6593078
Hoffman LA, Vilensky JA. Encephalitis lethargica: 100 years after the epidemic. Brain. 2017;140:2246–51. https://doi.org/10.1093/brain/awx177 .
doi: 10.1093/brain/awx177
pubmed: 28899018
Jang H, Boltz D, McClaren J, Pani AK, Smeyne M, Korff A, et al. Inflammatory effects of highly pathogenic H5N1 influenza virus infection in the CNS of mice. J Neurosci. 2012;32:1545–59. https://doi.org/10.1523/JNEUROSCI.5123-11.2012 .
doi: 10.1523/JNEUROSCI.5123-11.2012
pubmed: 22302798
pmcid: 3307392
Rohn TT, Catlin LW. Immunolocalization of influenza A virus and markers of inflammation in the human Parkinson’s disease brain. PLoS One. 2011;6:e20495. https://doi.org/10.1371/journal.pone.0020495 .
doi: 10.1371/journal.pone.0020495
pubmed: 21655265
pmcid: 3105060
Bantle CM, Rocha SM, French CT, Phillips AT, Tran K, Olson KE, et al. Astrocyte inflammatory signaling mediates alpha-synuclein aggregation and dopaminergic neuronal loss following viral encephalitis. Exp Neurol. 2021;346:113845. https://doi.org/10.1016/j.expneurol.2021.113845 .
doi: 10.1016/j.expneurol.2021.113845
pubmed: 34454938
pmcid: 9535678
Meng L, Shen L, Ji HF. Impact of infection on risk of Parkinson’s disease: a quantitative assessment of case-control and cohort studies. J Neurovirol. 2019;25:221–8. https://doi.org/10.1007/s13365-018-0707-4 .
doi: 10.1007/s13365-018-0707-4
pubmed: 30632012
Nerius M, Doblhammer G, Tamguney G. GI infections are associated with an increased risk of Parkinson’s disease. Gut. 2020;69:1154–6. https://doi.org/10.1136/gutjnl-2019-318822 .
doi: 10.1136/gutjnl-2019-318822
pubmed: 31201287
Berzero G, Basso S, Stoppini L, Palermo A, Pichiecchio A, Paoletti M, et al. Adoptive transfer of JC virus-specific T lymphocytes for the treatment of progressive multifocal leukoencephalopathy. Ann Neurol. 2021;89:769–79. https://doi.org/10.1002/ana.26020 .
doi: 10.1002/ana.26020
pubmed: 33459417
pmcid: 8248385
Byram SC, Carson MJ, DeBoy CA, Serpe CJ, Sanders VM, Jones KJ. CD4-positive T cell-mediated neuroprotection requires dual compartment antigen presentation. J Neurosci. 2004;24:4333–9. https://doi.org/10.1523/JNEUROSCI.5276-03.2004 .
doi: 10.1523/JNEUROSCI.5276-03.2004
pubmed: 15128847
pmcid: 2665301
Goddery EN, Fain CE, Lipovsky CG, Ayasoufi K, Yokanovich LT, Malo CS, et al. Microglia and perivascular macrophages act as antigen presenting cells to promote CD8 T cell infiltration of the brain. Front Immunol. 2021;12:726421. https://doi.org/10.3389/fimmu.2021.726421 .
doi: 10.3389/fimmu.2021.726421
pubmed: 34526998
pmcid: 8435747