The inhibitory effect of Fasciola hepatica antigens on induced LPS-DC activation correlates with a decrease in p38 and STAT3 phosphorylation and is independent on NF-?ÛB translocation

FALCÓN CRISTIAN; CARRANZA FRANCO; NUÑEZ NICOLÁS; CERVI LAURA

Capital Federal

Congreso; First French - Argentine Immunology Congress; 2010

sociedad argentina de inmunologia

The ability of different Fasciola hepatica (Fh) antigens to diminish the classical TLR ligand dendritic cell (DC) activation has been demonstrated. However, little is know about the signals used for this helminth to bias DC activation toward a tolerogenic profile. The objective of this work was to investigate the signals involved in the modulation of F.h total extract (TE) to decrease the LPS induced DC maturation when these cells are simultaneously exposed to both stimuli (T/L). The T/L treatment of bone marrow derived DC induced a significant increase in IL-10 production (determined by ELISA) (Student T test p<0.05) and ERK phosphorylation (determined by western blot) compared to LPS treated DC. Although IL-10 production was dependent on ERK phosphorylation, neither IL-10 blocking nor ERK inhibition restored the IL-12 levels of LPS treated DC. As a measure of NF-£eB activation, a crucial factor involved in the IL-12 production, we determined  I£eB degradation and Rel A translocation. The activation of these factors were not affected when DC were treated with T/L compared to LPS treated DC.  However, STAT-3 and p38 phosphorylation levels were lower in DC by T/L treatment than those presented in LPS-treated DC, suggesting that other signaling pathways different from NF-?ÛB could be affected by TE. Besides a Kunitz type molecule (KTM) purified from TE by FPLC, showed identical effects on MAPKs phosphorylation and  the NF-£eB activation than that exerted by TE. Overall, our data show that the modulatory effect  exerted by TE as well as KTM on LPS-activated DC is depending on the regulation of specific intracellular signals such as p38, ERK and STAT-3