Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected Neurons.
Animals
Antibodies, Protozoan
/ immunology
Antigens, Protozoan
/ immunology
Brain
/ cytology
Cell Line
Cells, Cultured
Histocompatibility Antigens Class I
/ genetics
Humans
Male
Mice
Mice, Inbred C57BL
Neurons
/ immunology
Protozoan Proteins
/ immunology
Toxoplasma
/ immunology
Toxoplasmosis, Cerebral
/ immunology
CD8 T cell
Toxoplasma gondii
antigen presentation
brain infection
encephalitis
neuroinflammation
neuron
parasite
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
11 06 2019
11 06 2019
Historique:
received:
10
09
2018
revised:
03
03
2019
accepted:
15
05
2019
entrez:
13
6
2019
pubmed:
13
6
2019
medline:
4
8
2020
Statut:
ppublish
Résumé
Control of CNS pathogens by CD8 T cells is key to avoid fatal neuroinflammation. Yet, the modalities of MHC I presentation in the brain are poorly understood. Here, we analyze the antigen presentation mechanisms underlying CD8 T cell-mediated control of the Toxoplasma gondii parasite in the CNS. We show that MHC I presentation of an efficiently processed model antigen (GRA6-OVA), even when not expressed in the bradyzoite stage, reduces cyst burden and dampens encephalitis in C57BL/6 mice. Antigen presentation assays with infected primary neurons reveal a correlation between lower MHC I presentation of tachyzoite antigens by neurons and poor parasite control in vivo. Using conditional MHC I-deficient mice, we find that neuronal MHC I presentation is required for robust restriction of T. gondii in the CNS during chronic phase, showing the importance of MHC I presentation by CNS neurons in the control of a prevalent brain pathogen.
Identifiants
pubmed: 31189109
pii: S2211-1247(19)30680-1
doi: 10.1016/j.celrep.2019.05.051
pmc: PMC8908772
mid: NIHMS1613015
pii:
doi:
Substances chimiques
Antibodies, Protozoan
0
Antigens, Protozoan
0
GRA6 protein, Toxoplasma gondii
0
Histocompatibility Antigens Class I
0
Protozoan Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3254-3268.e8Subventions
Organisme : NIAID NIH HHS
ID : R01 AI065537
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI093132
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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