Having already demostrated that parasite antigen profoundly alters the maturation and function of human dendritic cells, we have used live parasites (infective stage larvae [L3] or microfilariae) to examine, in a more physiological manner, the interaction between host and the parasite focussing in on those interactions that affect immunological outcome. First, using human Langerhans cells and microarray analysis, we have demonstrated that as few as 5 L3 can profoundly alter Langerhans' cell physiology. In contrast, similar numbers of L3s induce very few genes in more mature human dendritic cells (this in contrast to that induced by other parasites). Moreover, the L3s' effect on other cells in the innate immune pathway (naive T cells, NK cells, monocytes) are profoundly different, with the induction of proinflammatory cascades and apoptosis. The induction of apoptosis appears to be a common mechanism by which the filarial parasites influences the host response. Once the immune response to the parasitic infection is established, downregulatory mechanims are induced. The elucidate the mehansims underlying this downregulation seen in chronic filarial/helminth infection, we have identified pathways that utilize CTLA4 as well as regulatotory T cells (through IL-10) as those that modulate the antigen-specific immune response.
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