Artículo
IL-17RA-signaling modulates CD8+ T Cell survival and exhaustion during trypanosoma cruzi infection
Tosello Boari, Jimena
; Araujo Furlan, Cintia Liliana
; Fiocca Vernengo, Facundo
; Rodriguez, Constanza
; Ramello, María Cecilia
; Amezcua Vesely, Maria Carolina
; Gorosito Serran, Melisa
; Nuñez, Nicolás G.; Richer, Wilfrid; Piaggio, Eliane; Montes, Carolina Lucia
; Gruppi, Adriana
; Acosta Rodriguez, Eva Virginia
Fecha de publicación:
10/2018
Editorial:
Frontiers Media S.A.
Revista:
Frontiers in Immunology
ISSN:
1664-3224
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
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Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Citación
Tosello Boari, Jimena; Araujo Furlan, Cintia Liliana; Fiocca Vernengo, Facundo; Rodriguez, Constanza; Ramello, María Cecilia; et al.; IL-17RA-signaling modulates CD8+ T Cell survival and exhaustion during trypanosoma cruzi infection; Frontiers Media S.A.; Frontiers in Immunology; 9; 10-2018; 1-18
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