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IL-17RA signaling reduces inflammation and mortality during Trypanosoma cruzi infection by recruiting suppressive IL-10-producing neutrophils.
Tosello Boari, Jimena; Amezcua Vesely, María Carolina; Bermejo, Daniela Andrea; Ramello, Maria Cecilia; Montes, Carolina Lucía; Cejas, Hugo; Gruppi, Adriana; Acosta Rodríguez, Eva Virginia.
Afiliação
  • Tosello Boari J; Centro de Investigaciones en Bioquímica Clínica e Inmunología-CIBICI-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
PLoS Pathog ; 8(4): e1002658, 2012.
Article em En | MEDLINE | ID: mdl-22577359
Members of the IL-17 cytokine family play an important role in protection against pathogens through the induction of different effector mechanisms. We determined that IL-17A, IL-17E and IL-17F are produced during the acute phase of T. cruzi infection. Using IL-17RA knockout (KO) mice, we demonstrate that IL-17RA, the common receptor subunit for many IL-17 family members, is required for host resistance during T. cruzi infection. Furthermore, infected IL-17RA KO mice that lack of response to several IL-17 cytokines showed amplified inflammatory responses with exuberant IFN-γ and TNF production that promoted hepatic damage and mortality. Absence of IL-17RA during T. cruzi infection resulted in reduced CXCL1 and CXCL2 expression in spleen and liver and limited neutrophil recruitment. T. cruzi-stimulated neutrophils secreted IL-10 and showed an IL-10-dependent suppressive phenotype in vitro inhibiting T-cell proliferation and IFN-γ production. Specific depletion of Ly-6G+ neutrophils in vivo during T. cruzi infection raised parasitemia and serum IFN-γ concentration and resulted in increased liver pathology in WT mice and overwhelming wasting disease in IL-17RA KO mice. Adoptively transferred neutrophils were unable to migrate to tissues and to restore resistant phenotype in infected IL-17RA KO mice but migrated to spleen and liver of infected WT mice and downregulated IFN-γ production and increased survival in an IL-10 dependent manner. Our results underscore the role of IL-17RA in the modulation of IFN-γ-mediated inflammatory responses during infections and uncover a previously unrecognized regulatory mechanism that involves the IL-17RA-mediated recruitment of suppressive IL-10-producing neutrophils.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trypanosoma cruzi / Transdução de Sinais / Doença de Chagas / Receptores de Interleucina-17 / Neutrófilos Limite: Animals Idioma: En Revista: PLoS Pathog Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trypanosoma cruzi / Transdução de Sinais / Doença de Chagas / Receptores de Interleucina-17 / Neutrófilos Limite: Animals Idioma: En Revista: PLoS Pathog Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos