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

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

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The IL-17 family contributes to host defense against many intracellular pathogens by mechanisms that are not fully understood.CD8+ T lymphocytes are key elements argan oil pure purple 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 magnitude of CD8+ T cell responses and parasite control in these mice.

Adoptive transfer experiments animed aniflex complete established that IL-17RA-signaling is intrinsically required for the proper maintenance of functional effector CD8+ T cells.Altogether, our results identify IL-17RA and IL-17A as critical factors for sustaining CD8+ T cell immunity to T.cruzi.