The inhibitory effect of Fasciola hepatica antigens on LPS maturated dendritic cells correlates with a decrease in p38 and STAT3 expression, and is independent on NF-ƒÛB traslocation

FALCON C; CARRANZA F; CERVI L

Congreso; First French-Argentine Immunology Congress LVIII Reunión científica de la Sociedad Argentina de Inmunología.; 2010

  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 involved in the capacity of this helminth to bias DC activation toward a tolerogenic profile. The goal of this work was to investigate some signals implicated in the decrease of pro-inflammatory cytokines observed when DC are simultaneously exposed to a F.h total extract together with LPS (T/L)  compared to LPS-treated DC. We have studied, IL-10 production, the phosphorilation levels of the MAPkinases p38 and ERK as well as the activation of the nuclear factors NF-kB and STAT3, all components of the immune response involved in the modulation of pro-inflammatory cytokines. The T/L treatment of DC induced a significant increase in IL-10 production (Student T test p<0.05) and ERK phosphorylation 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 phosphorilation levels were lower in DC by T/L treatment than those presented in LPS-treated DC, suggesting that other signaling pathways different from NF-kB could be affected by TE. Overall, our data show that the inhibitory effect on pro-inflammatory cytokine production exerted by  TE on LPS-activated DC is depending on the modulation of specific intracellular signals such as p38 and ERK. Additionally we also demonstrated the tight correlation between a strong phosphorilation of ERK and the increased amount of IL-10 produced by T/L treatment, seems to be a independent regulatory pathway which is not responsible for the inhibition in  IL-12 production.