LOW MOLECULAR WEIGHT PROTEINS OF FASCIOLA HEPATICA IMPAIR DENDRITIC CELLS ABILITY TO INDUCE T CELL INFLAMMATORY RESPONSES: CRITICAL ROLE FOR A KUNITZ TYPE MOLECULE

. CERVI L.; CELIAS D; MOTRAN C; C R FALCON

Córdoba

Congreso; XLI Reunion Anual de la Sociedad Argentina de Inmunología; 2013

SAI

The ability of different Fasciola hepatica (Fh) antigens to reduce Toll-like receptor-dendritic cells (TLR-DC) activation has been demonstrated. However, the complete scenario of immunoevasion induced by this parasite remains unclear. We previously demonstrated that Fh total extract (TE) decreased the pro- inflammatory cytokines levels in LPS-activated DC and that among the different proteins contained in TE, a fraction lower than 10kDa (F<10kDa) showed an inhibitory activity similar to total extract. The aim of this work was to study the ability of bone marrow derived DC from Balb/c mice treated with F<10kDa to modulate adaptive allogeneic responses and identify the protein/s responsible/s of suppression on DC activation. Here, we show that the TE or F<10kDa treatment improved the ability of immature DC to induce de novo allogeneic CD4+CD25+Foxp3+ T cells in allogeneic culture with splenocytes from transgenic C57BL/6 EGPF-Foxp3 mice. Besides, the treatment of DC with F<10kDa plus LPS (F<10/L) induced regulatory IL-27 dependent mechanisms that diminished Th1 and Th17 allogeneic responses. The significance of this work was the identification of a Kunitz type molecule from F. hepatica (Fh-KTM) contained in F<10kDa as an immunosuppressor protein, which was able to decrease the DC activation and their ability to activate T cells. In this regard, DC treated with recombinant Fh-KTM plus LPS were less able to induce IL-6 or TNF secretion (p<0.05) and stimulate IFN-ã and IL-17 production by allogeneic splenocytes compared to LPS maturated DC (p<0.02). Together these data suggest that the Fh-KTM has a relevant role in the immunoevasion mechanisms induced by the parasite, and may become a new target molecule to reduce undesirable inflammatory responses