Fasciola hepatica antigens modulate dendritic cells activation and metabolism

CERVI L; MOTRÁN C; MASIH DT

Cordoba, Argentina

Congreso; VII Latin American Congress of Immunology; 2005

Sociedad Argentina de Inmunología

It is well known that dendritic cells (DC) activation plays a role in T cell response development. In addition, antigens from helminths are able to modulate DC activation, but is not clear how this can affect Th2 development. To determine the capacity of excretory-secretory antigen of F. hepatica (ESA) to modulate the activation and metabolism in DC, murine bone marrow-derived DC were pulsed with medium, ESA, LPS or ESA plus LPS for 18 h and the expression of MHCII, CD80, CD86, and CD40 were assessed by FACS. In addition, the expression of two enzymes with immunomodulatory properties in DC, Indoleamine 2-3, dioxygenase (IDO, involved in tolerance and Th2 response induction) and arginase, were also evaluated by Western blot and activity respectively. ESA downregulates the expression of MHCII, CD80, CD86, and CD40 molecules on immature, and LPS mature DC, being the highest effect on CD40 expression  (from 56% to 7%). Moreover, ESA was able to increase IDO protein expression and arginase activity on immature and LPS mature DC, compared with medium alone- or LPS-treated DC. Our results show that ESA from F. hepatica, the first group of antigens that immune system  contact after the infection, are able to modulate the activation  of DC and may play a role in the outcome of adaptative immune response. In addition, this is the first report demonstrating the ability of helminths antigens to induce IDO expression in DC. Besides, the ability of IDO expressing cells to selectively induce apoptosis of Th1 cells, arises an unexplored role for IDO in Th2 development in helminth infection.