Impairment in Natural Killer Cells Editing of Immature Dendritic Cells by Infection with a Virulent Trypanosoma cruzi Population

BATALLA, ESTELA I; PINO-MARTINEZ, AGUSTINA MARIA; PONCINI, CAROLINA V; DUFFY, TOMAS; SCHIJMAN, ALEJANDRO G.; GONZALEZ-CAPPA , STELLA MARIS; ALBA SOTO, CATALINA D.

JOURNAL OF INNATE IMMUNITY

KARGER

Lugar: Basel; Año: 2013 vol. 5 p. 494 - 504

1662-811X

Abstract Early interactions between natural killer (NK) cells and dendritic cells (DC) shape the immune response at the frontier of innate and adaptive immunity. Activated NK cells participate in maturation or deletion of DCs that remain immature. We previously demonstrated that infection with a high virulence (HV) population of the protozoan parasite T. cruzi downmodulates DC maturation and T cell-activation capacity. Here, we evaluated the participation of NK cells in regulating the maturation level of the DCs. Shortly after infection with HV, DCs with poor maturation status begin to accumulate in the spleen of mice. Although infection induces NK cells cytotoxicity and cytokine production, NK cells from mice infected with HV exhibit a reduced ability to lyse and fail to induce maturation of bone marrow-derived immature DCs. 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 HV infected IL-10KO mice. These results suggest that infection with a virulent T. cruzi strain alters NK-mediated regulation of the adaptive immune response induced by DCs. This regulatory circuit might lead to parasite persistence but can also limit the induction of a vigorous tissue damaging T cell response.