Impairment of Natural Killer (NK) Cells Editing of Immature Dendritic Cells (DC) by Infection with a virulent Trypanosoma cruzi population

BATALLA E; PINO MARTÍNEZ AM; PONCINI C; DUFFY T; SCHIJMAN A.G; GONZÁLEZ CAPPA SM; ALBA SOTO CD

Ouro Preto, Brasil

Simposio; Keystone Symposium on The Innate Immune Response in the Pathogenesis of Infectious Disease. Evento Internacional.; 2013

Early interactions between NK cells and DCs shape the immune response at the frontier of innate and adaptive immunity. Activated NK cells participate in DCs maturation or deletion of DCs that remain immature. Chagas? disease, caused by the protozoan Trypanosoma cruzi (T.cruzi), varies from a relatively benign asymptomatic form to digestive or fatal cardiac course. Diversity among T. cruzi isolates might delineate the host immune response and disease outcome. We previously demonstrated that a virulent T.cruzi population downmodulates DC maturation and T cell stimulation. Here, we addressed the role of NK cells in regulating the maturation level of the DC pool. Shortly after infection with virulent T.cruzi population, DCs with poor maturation status begin to accumulate in the spleen of mice. Although T. cruzi infection induces NK cells cytotoxic potential and cytokine production, NK cells from mice infected with the high virulent population exhibit a reduced ability to lyse and fail to induce maturation of bone marrow-derived immature DCs. Finally, NK mediated lysis of immature DCs is restored by in vitro blockade of the IL-10 receptor during NK-DC interaction or when NK cells are obtained from infected IL-10 deficient mice. Altogether, these results suggest that infection with a T.cruzi population of high virulence impairs NK cell capacity to modulate the strength of adaptive immune response by DCs. This immunoregulatory mechanism mediated by IL-10 which might delay the induction of a vigorous tissue damaging T cell response but to the cost of parasite persistence.