Role of T cells during the cerebral infection with Trypanosoma brucei.
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
22
03
2021
accepted:
25
08
2021
revised:
21
10
2021
pubmed:
30
9
2021
medline:
15
12
2021
entrez:
29
9
2021
Statut:
epublish
Résumé
The infection by Trypanosoma brucei brucei (T.b.b.), a protozoan parasite, is characterized by an early-systemic stage followed by a late stage in which parasites invade the brain parenchyma in a T cell-dependent manner. Here we found that early after infection effector-memory T cells were predominant among brain T cells, whereas, during the encephalitic stage T cells acquired a tissue resident memory phenotype (TRM) and expressed PD1. Both CD4 and CD8 T cells were independently redundant for the penetration of T.b.b. and other leukocytes into the brain parenchyma. The role of lymphoid cells during the T.b.b. infection was studied by comparing T- and B-cell deficient rag1-/- and WT mice. Early after infection, parasites located in circumventricular organs, brain structures with increased vascular permeability, particularly in the median eminence (ME), paced closed to the sleep-wake regulatory arcuate nucleus of the hypothalamus (Arc). Whereas parasite levels in the ME were higher in rag1-/- than in WT mice, leukocytes were instead reduced. Rag1-/- infected mice showed increased levels of meca32 mRNA coding for a blood /hypothalamus endothelial molecule absent in the blood-brain-barrier (BBB). Both immune and metabolic transcripts were elevated in the ME/Arc of WT and rag1-/- mice early after infection, except for ifng mRNA, which levels were only increased in WT mice. Finally, using a non-invasive sleep-wake cycle assessment method we proposed a putative role of lymphocytes in mediating sleep alterations during the infection with T.b.b. Thus, the majority of T cells in the brain during the early stage of T.b.b. infection expressed an effector-memory phenotype while TRM cells developed in the late stage of infection. T cells and parasites invade the ME/Arc altering the metabolic and inflammatory responses during the early stage of infection and modulating sleep disturbances.
Identifiants
pubmed: 34587172
doi: 10.1371/journal.pntd.0009764
pii: PNTD-D-21-00411
pmc: PMC8530334
doi:
Substances chimiques
Homeodomain Proteins
0
RAG-1 protein
128559-51-3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0009764Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
J Exp Med. 2016 Jul 25;213(8):1571-87
pubmed: 27377586
Front Immunol. 2018 Dec 11;9:2877
pubmed: 30619260
J Biol Chem. 1994 Sep 23;269(38):23757-63
pubmed: 8089148
Brain Behav Immun. 2005 Mar;19(2):127-37
pubmed: 15664785
Nat Med. 2015 Jul;21(7):688-97
pubmed: 26121195
Brain Res Bull. 2019 Feb;145:59-74
pubmed: 30016726
Nature. 2018 Oct;562(7725):63-68
pubmed: 30232458
J Biol Chem. 2011 Jul 29;286(30):26873-87
pubmed: 21622562
Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19408-13
pubmed: 20962277
Brain Res Rev. 2007 Nov;56(1):119-47
pubmed: 17659349
J Neurosci. 2013 Sep 4;33(36):14288-300
pubmed: 24005282
Am J Trop Med Hyg. 2010 Jun;82(6):983-90
pubmed: 20519589
Brain Res Bull. 1995;37(2):123-9
pubmed: 7606487
J Sleep Res. 2021 Jun;30(3):e13187
pubmed: 32902030
Nat Commun. 2019 Feb 19;10(1):837
pubmed: 30783092
J Exp Med. 2004 Feb 16;199(4):559-65
pubmed: 14769854
J Neurosci. 2009 Mar 25;29(12):3885-96
pubmed: 19321785
Acta Neuropathol. 2010 Dec;120(6):689-705
pubmed: 20830478
Infect Immun. 2002 Jan;70(1):185-91
pubmed: 11748181
Neuropathol Appl Neurobiol. 2009 Jun;35(3):232-46
pubmed: 19473292
Nature. 2013 Apr 11;496(7444):238-42
pubmed: 23535595
Front Cell Neurosci. 2015 Mar 12;9:80
pubmed: 25814932
J Biol Rhythms. 2012 Feb;27(1):48-58
pubmed: 22306973
Cell Metab. 2013 Apr 2;17(4):607-17
pubmed: 23562080
Lancet Neurol. 2015 Mar;14(3):318-28
pubmed: 25728441
J Neurosci Res. 1988 Sep;21(1):56-61
pubmed: 3216412
Autoimmun Rev. 2018 Sep;17(9):906-911
pubmed: 30005862
Eur J Immunol. 1994 Sep;24(9):2213-8
pubmed: 7916297
Front Neuroanat. 2018 Feb 27;12:13
pubmed: 29535612
Nature. 1991 Sep 12;353(6340):180-4
pubmed: 1832488
J Infect Dis. 2012 Jan 15;205(2):320-32
pubmed: 22116836
Curr Top Microbiol Immunol. 2002;265:227-57
pubmed: 12014192
Nat Immunol. 2015 Apr;16(4):406-14
pubmed: 25706747
Nat Neurosci. 2011 Oct 09;14(11):1418-20
pubmed: 21983682
Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17872-9
pubmed: 20923878
Prog Neurobiol. 2010 Jun;91(2):152-71
pubmed: 19995590
J Immunol. 2014 Apr 1;192(7):2961-4
pubmed: 24600038
Cell. 2015 May 7;161(4):737-49
pubmed: 25957682
PLoS Negl Trop Dis. 2016 Dec 21;10(12):e0005242
pubmed: 28002454
Nat Protoc. 2014 Jan;9(1):209-22
pubmed: 24385150
Neuroscience. 2015 Apr 2;290:185-95
pubmed: 25595977
J Autoimmun. 2019 Jun;100:1-6
pubmed: 30948158
Neuron. 2020 Jul 22;107(2):306-319.e9
pubmed: 32407670
J Biol Chem. 1996 Dec 20;271(51):32529-37
pubmed: 8955077
PLoS Pathog. 2016 Feb 25;12(2):e1005442
pubmed: 26915097
J Infect Dis. 2009 Nov 15;200(10):1556-65
pubmed: 19827943
J Clin Invest. 2004 Sep;114(5):689-94
pubmed: 15343387
J Virol. 2016 May 27;90(12):5785-96
pubmed: 27053560
Science. 2003 Apr 11;300(5617):339-42
pubmed: 12690202
Nat Rev Immunol. 2015 Aug;15(8):486-99
pubmed: 26205583
Front Neurosci. 2015 Oct 27;9:390
pubmed: 26578857
Nat Commun. 2013;4:2049
pubmed: 23804023
Front Biosci. 2008 May 01;13:4529-43
pubmed: 18508527
Neurosci Lett. 2011 Jan 7;487(2):187-90
pubmed: 20951768
PLoS Negl Trop Dis. 2017 Aug 18;11(8):e0005854
pubmed: 28821016
Cell Metab. 2015 Jan 6;21(1):65-80
pubmed: 25565206
J Comp Neurol. 2013 Oct 15;521(15):3389-405
pubmed: 23649873
Nat Immunol. 2013 Dec;14(12):1294-301
pubmed: 24162776
Physiol Genomics. 2007 Jan 17;28(2):232-8
pubmed: 16985007
Nature. 2012 Feb 29;483(7388):227-31
pubmed: 22388819
Nature. 1992 Oct 29;359(6398):843-5
pubmed: 1279431
Sleep. 2008 Mar;31(3):348-54
pubmed: 18363311
Immunol Lett. 1995 Feb;45(1-2):53-60
pubmed: 7622189