Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy.
Antifungal therapy
Cryptococcus neoformans
Flow cytometry
Fungal meningitis
HIV
Intrathecal immunity
Journal
BMC neurology
ISSN: 1471-2377
Titre abrégé: BMC Neurol
Pays: England
ID NLM: 100968555
Informations de publication
Date de publication:
03 Jul 2024
03 Jul 2024
Historique:
received:
27
06
2023
accepted:
21
06
2024
medline:
4
7
2024
pubmed:
4
7
2024
entrez:
3
7
2024
Statut:
epublish
Résumé
Cryptococcal meningitis (CM) is a severe fungal disease in immunocompromised patients affecting the central nervous system (CNS). Host response and immunological alterations in the cerebrospinal fluid (CSF) after invasion of Cryptococcus neoformans to the central nervous system have been investigated before but rigorous and comprehensive studies examining cellular changes in the CSF of patients with cryptococccal meningitis are still rare. We retrospectively collected CSF analysis and flow cytometry data of CSF and blood in patients with CM (n = 7) and compared them to HIV positive patients without meningitis (n = 13) and HIV negative healthy controls (n = 7). Within the group of patients with CM we compared those with HIV infection (n = 3) or other immunocompromised conditions (n = 4). Flow cytometry analysis revealed an elevation of natural killer cells and natural killer T cells in the CSF and blood of HIV negative patients with CM, pointing to innate immune activation in early stages after fungal invasion. HIV positive patients with CM exhibited stronger blood-CSF-barrier disruption. Follow-up CSF analysis over up to 150 days showed heterogeneous cellular courses in CM patients with slow normalization of CSF after induction of antifungal therapy.
Identifiants
pubmed: 38961320
doi: 10.1186/s12883-024-03742-9
pii: 10.1186/s12883-024-03742-9
doi:
Substances chimiques
Antifungal Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
229Informations de copyright
© 2024. The Author(s).
Références
Fisher KM, et al. Cryptococcal meningitis: a review for emergency clinicians. Intern Emerg Med. 2021;16(4):1031–42.
doi: 10.1007/s11739-020-02619-2
pubmed: 33420904
Liu TB, Perlin DS, Xue C. Molecular mechanisms of cryptococcal meningitis. Virulence. 2012;3(2):173–81.
doi: 10.4161/viru.18685
pubmed: 22460646
pmcid: 3396696
Zaragoza O. Basic principles of the virulence of Cryptococcus. Virulence. 2019;10(1):490–501.
doi: 10.1080/21505594.2019.1614383
pubmed: 31119976
pmcid: 6550552
Robertson EJ, et al. Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis. J Infect Dis. 2014;209(1):74–82.
doi: 10.1093/infdis/jit435
pubmed: 23945372
Alanazi AH, Adil MS, Lin X, Chastain DB, Henao-Martínez AF, Franco-Paredes C, Somanath PR. Elevated intracranial pressure in cryptococcal meningoencephalitis: examining old, new, and promising drug therapies. Pathogens. 2022;11(7):783. https://doi.org/10.3390/pathogens11070783 .
Colombo AC, Rodrigues ML. Fungal colonization of the brain: anatomopathological aspects of neurological cryptococcosis. An Acad Bras Cienc. 2015;87(2 Suppl):1293–309.
doi: 10.1590/0001-3765201520140704
pubmed: 26247147
Scriven JE, et al. The CSF Immune Response in HIV-1-Associated Cryptococcal Meningitis: Macrophage Activation, Correlates of Disease Severity, and Effect of Antiretroviral Therapy. J Acquir Immune Defic Syndr. 2017;75(3):299–307.
doi: 10.1097/QAI.0000000000001382
pubmed: 28346317
pmcid: 5469563
Scriven JE, et al. Flow Cytometry To Assess Cerebrospinal Fluid Fungal Burden in Cryptococcal Meningitis. J Clin Microbiol. 2016;54(3):802–4.
doi: 10.1128/JCM.03002-15
pubmed: 26719441
pmcid: 4767993
Heming M, et al. Immune Cell Profiling of the Cerebrospinal Fluid Provides Pathogenetic Insights Into Inflammatory Neuropathies. Front Immunol. 2019;10:515.
doi: 10.3389/fimmu.2019.00515
pubmed: 30984164
pmcid: 6448021
Heming M, et al. Supporting the differential diagnosis of connective tissue diseases with neurological involvement by blood and cerebrospinal fluid flow cytometry. J Neuroinflammation. 2023;20(1):46.
doi: 10.1186/s12974-023-02733-w
pubmed: 36823602
pmcid: 9951507
Peterson RA, Cavanaugh JE. Ordered quantile normalization: a semiparametric transformation built for the cross-validation era. J Appl Stat. 2020;47(13–15):2312–27.
doi: 10.1080/02664763.2019.1630372
pubmed: 35707424
Lê S, Josse J, Husson F. FactoMineR: An R Package for Multivariate Analysis. J Stat Softw. 2008;25(1):1–18.
doi: 10.18637/jss.v025.i01
Robin X, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011;12:77.
doi: 10.1186/1471-2105-12-77
pubmed: 21414208
pmcid: 3068975
Casadevall A, et al. The capsule of Cryptococcus neoformans. Virulence. 2019;10(1):822–31.
doi: 10.1080/21505594.2018.1431087
pubmed: 29436899
Coelho C, Bocca AL, Casadevall A. The tools for virulence of Cryptococcus neoformans. Adv Appl Microbiol. 2014;87:1–41.
doi: 10.1016/B978-0-12-800261-2.00001-3
pubmed: 24581388
Maziarz EK, P.J. Cryptococcosis. Infect Dis Clin North Am. 2016;30:179–206.
doi: 10.1016/j.idc.2015.10.006
pubmed: 26897067
pmcid: 5808417
Hasbun R. Progress and Challenges in Bacterial Meningitis: A Review. JAMA. 2022;328(21):2147–54.
doi: 10.1001/jama.2022.20521
pubmed: 36472590
Lepennetier G, et al. Cytokine and immune cell profiling in the cerebrospinal fluid of patients with neuro-inflammatory diseases. J Neuroinflammation. 2019;16(1):219.
doi: 10.1186/s12974-019-1601-6
pubmed: 31727097
pmcid: 6857241
Toborek M, et al. Mechanisms of the blood-brain barrier disruption in HIV-1 infection. Cell Mol Neurobiol. 2005;25(1):181–99.
doi: 10.1007/s10571-004-1383-x
pubmed: 15962513
Sun Y, et al. Disruption of blood-brain barrier: effects of HIV Tat on brain microvascular endothelial cells and tight junction proteins. J Neurovirol. 2023;29(6):658–68.
doi: 10.1007/s13365-023-01179-3
pubmed: 37899420
Rahimy E, et al. Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy. J Infect Dis. 2017;215(7):1132–40.
doi: 10.1093/infdis/jix013
pubmed: 28368497
pmcid: 5426376
Vivier E, et al. Functions of natural killer cells. Nat Immunol. 2008;9(5):503–10.
doi: 10.1038/ni1582
pubmed: 18425107
Schmidt S, Tramsen L, Lehrnbecher T. Natural Killer Cells in Antifungal Immunity. Front Immunol. 2017;8:1623
doi: 10.3389/fimmu.2017.01623
pubmed: 29213274
pmcid: 5702641
Galvez, N.M.S, et al. Type I Natural Killer T Cells as Key Regulators of the Immune Response to Infectious Diseases. Clin Microbiol Rev,. 2021;34(2):e00232.
doi: 10.1128/CMR.00232-20
pubmed: 33361143
Cooper M.A, Fehniger T.A, Caligiuri M.A. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22(11):633–40.
doi: 10.1016/S1471-4906(01)02060-9
pubmed: 11698225
Meya DB, et al. Cellular immune activation in cerebrospinal fluid from ugandans with cryptococcal meningitis and immune reconstitution inflammatory syndrome. J Infect Dis. 2015;211(10):1597–606.
doi: 10.1093/infdis/jiu664
pubmed: 25492918