Role of the parasite-derived prostaglandin D-2 in the inhibition of epidermal Langerhans cell migration during schistosomiasis infection

Epidermal Langerhans cells (LCs) play a key role in immune defense mechanis ms and ill numerous immunological disorders. In this report, we show that p ercutaneous infection oi C57BL/b mice with the helminth parasite Schistosom a mansoni leads to the activation of LCs but. surprisingly, to their retent ion in tile epidermis. Moreover, using all experimental model of LC migrati on induced by tumor necrosis factor (TNF)-alpha, we show that parasites tra nsiently impair the departure of LCs from the epidermis and their subsequen t accumulation as dendritic cells in the draining lymph nodes, The inhibito ry effect is mediated by soluble lipophilic factors released by the parasit es and not by host-derived antiinflammatory cytokines, such as interleukin- li). We find that prostaglandin (PG)D-2, but not the other major eicosanoid s produced by the parasites, specifically impedes the TNF-alpha -triggered migration of L.Cs through the adenylate cyclase-coupled PGD(2) receptor (DP receptor), Moreover, the potent DP receptor antagonist BW A868C restores L C migration in infected mice. Finally, in a model of contact allergen-induc ed LC migration, we show; that activation of the DP receptor not only inhib its LC emigration but also dramatically reduces the contact hypersensitivit y responses after challenge, taken together, we propose that the inhibition of LC migration could represent all additional stratagem for the schistoso mes to escape the host immune system and that PGD, may play a key role in t he control of cutaneous immune responses.