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IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During Trypanosoma cruzi Infection.
- Source :
-
Frontiers in immunology [Front Immunol] 2018 Oct 11; Vol. 9, pp. 2347. Date of Electronic Publication: 2018 Oct 11 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- 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 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 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 .
- Subjects :
- Adoptive Transfer
Animals
Apoptosis
Cell Survival
Chagas Disease microbiology
Cytokines metabolism
Female
Host-Pathogen Interactions genetics
Host-Pathogen Interactions immunology
Immunomodulation genetics
Interleukin-17 metabolism
Lymphocyte Activation genetics
Lymphocyte Activation immunology
Lymphocyte Count
Male
Mice
Mice, Knockout
Receptors, Interleukin-17 deficiency
Transcription, Genetic
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Chagas Disease immunology
Chagas Disease metabolism
Receptors, Interleukin-17 metabolism
Signal Transduction
Trypanosoma cruzi immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 30364284
- Full Text :
- https://doi.org/10.3389/fimmu.2018.02347