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

PLOS PATHOGENS

PLos Pathogen

Año: 2012 vol. 8

1553-7366

embers 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+ neutrop