Dendritic Cells (DC) devoid of IL-10 Confer Enhanced Protection against a Protozoan Parasite by DCBased Immunotherapy

AGUSTINA PINO MARTINEZ; MARIA ELISA SOLANA; CRISTIAN GABRIEL MIRANDA; CAROLINA VERONICA PONCINI; STELLA MARIS GONZALEZ CAPPA; CATALINA DIRNEY ALBA SOTO

Viña del Mar, Chile

Congreso; 9thLatin American Congress of Immunology; 2009

Sociedad Latinoamericana de Inmunología

Effective vaccination strategies rely on the knowledge of factors that influence the generation of optimal immune responses by DC. Previously, we demonstrated that murine infection with Trypanosoma cruzi, interferes in vivo and in vitro the maturation/activation of DC, their T cell stimulatory capacity and induces them to secrete immunoregulatory cytokines IL-10 and TGF-beta. In vitro neutralization of endogenous IL-10 on DC reverts their regulatory phenotype. We tested whether DC devoid of IL-10 (IL-10KO-DC) were superior to conventional DC (WT-DC) in triggering immunity against T. cruzi. DC (from WT and IL-10KO mice) were generated and pulsed for 24 hs with T. cruzi trypomastigote lysate. Mice were adoptively transferred with pulsed DC and challenged with T. cruzi.  Upon antigen pulsing, both IL-10KO and WT-DC enhanced expression of MHC class II, CD80, CD86 and CD40 and secretion of IL-6. However, only IL-10KO-DC produced IL-12 and conversely, WT-DC secreted IL-10 but no IL-12. Immunotherapy with IL-10KO-DC induced 100% protection compared to controls (unpulsed IL-10KO-DC:0%; Ag pulsed WT-DC:0%; unpulsed WT-DC:20%; PBS:0%) with lower parasitemia levels at the peak of infections (P<0.05). Strategies based on the suppression of DC´s IL-10 production appear to be relevant to improve of protection against T. cruzi by immunotherapy.