IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During Trypanosoma cruzi Infection

TOSELLO BOARI, JIMENA; ARAUJO FURLAN, CINTIA L.; FIOCCA VERNENGO, FACUNDO; RODRIGUEZ, CONSTANZA; RAMELLO, MARÍA C.; AMEZCUA VESELY, MARÍA C.; GOROSITO SERRÁN, MELISA; NUÑEZ, NICOLÁS G.; RICHER, WILFRID; PIAGGIO, ELIANE; MONTES, CAROLINA L.; GRUPPI, ADRIANA; ACOSTA RODRÍGUEZ, EVA V.

Frontiers in Immunology

Frontiers Media S.A.

Año: 2018 vol. 9

he IL-17 family contributes to host defense against many intracellular pathogens by mechanisms that are not fully understood. CD8+ T lymphocytes are key elements against intracellular microbes, and their survival and ability to mount cytotoxic responses are orchestrated by several cytokines. Here, we demonstrated that IL-17RA-signaling cytokines sustain pathogen-specific CD8+ T cell immunity. The absence of IL-17RA and IL-17A/F during Trypanosoma cruzi infection resulted in increased tissue parasitism and reduced frequency of parasite-specific CD8+ T cells. Impaired IL-17RA-signaling in vivo increased apoptosis of parasite-specific CD8+ T cells, while in vitro recombinant IL-17 down-regulated the pro-apoptotic protein BAD and promoted the survival of activated CD8+ T cells. Phenotypic, functional, and transcriptomic profiling showed that T. cruzi-specific CD8+ T cells derived from IL-17RA-deficient mice presented features of cell dysfunction. PD-L1 blockade partially restored the magn