Cutting Edge: Augmenting Muscle MHC Expression Enhances Systemic Pathogen Control at the Expense of T Cell Exhaustion.
J Immunol
; 205(3): 573-578, 2020 08 01.
Article
em En
| MEDLINE
| ID: mdl-32591392
ABSTRACT
Myocytes express low levels of MHC class I (MHC I), perhaps influencing the ability of CD8+ T cells to efficiently detect and destroy pathogens that invade muscle. Trypanosoma cruzi infects many cell types but preferentially persists in muscle, and we asked if this tissue-dependent persistence was linked to MHC expression. Inducible enhancement of skeletal muscle MHC I in mice during the first 20 d of T. cruzi infection resulted in enhanced CD8-dependent reduction of parasite load. However, continued overexpression of MHC I beyond 30 d ultimately led to a collapse of systemic parasite control associated with immune exhaustion, which was reversible in part by blocking PD-1PD-L1 interactions. These studies demonstrate a surprisingly strong and systemically dominant effect of skeletal muscle MHC expression on maintaining T cell function and pathogen control and argue that the normally low MHC I expression in skeletal muscle is host protective by allowing for pathogen control while preventing immune exhaustion.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trypanosoma cruzi
/
Antígenos de Histocompatibilidade Classe I
/
Regulação da Expressão Gênica
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Doença de Chagas
/
Fibras Musculares Esqueléticas
/
Linfócitos T CD8-Positivos
Tipo de estudo:
Health_economic_evaluation
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article