A Role for Parasite-Induced PGE2 in IL-10-Mediated Host Immunoregulation by Skin Stage Schistosomula ofSchistosoma mansoni

Abstract

Significant quantities of PGE2 were produced by cercariae of Schistosoma mansoni following incubation with linoleic acid, a free fatty acid found on the surface of the skin. Cyclooxygenase (COX) 2 inhibitors failed to block this PGE2 production, suggesting that a different biochemical pathway may be involved in the production of PGE2 by the parasite. In addition, the parasites were also able to induce PGE2 and IL-10 from human and mouse keratinocytes. Analysis of mouse skin during skin migratory phases of infection confirmed these in vitro observations. COX2 inhibitors blocked the parasite-induced PGE2 and IL-10 from keratinocytes. Further analysis of the parasite secretions showed that the PGE2/IL-10-inducing effect was associated with a fraction <30 kDa molecular size. Addition of this fraction or parasite-stimulated keratinocyte culture supernatant to Con A-stimulated spleen cells resulted in the suppression of cell proliferation. This effect could be blocked by anti-IL-10 treatment. In sharp contrast, attenuation of the parasites with γ-irradiation significantly abrogated their ability to induce PGE2 or IL-10 from skin cells. Significance of IL-10 in host immunoregulation by skin stage schistosomula of S. mansoni was further confirmed by using IL-10-deficient mice. In these mice the normal subdued cutaneous reaction to the parasite was absent. Instead, a prominent cellular reaction occurred around the parasite, and there was considerable delay in parasitic migration through the skin. Thus these results suggest a key role for parasite-induced PGE2 in IL-10-dependent down-regulation of host immune responses in the skin.

Cercarial Dermatitis Caused by Bird Schistosomes Comprises Both Immediate and Late Phase Cutaneous Hypersensitivity Reactions

“…IL-10 is in addition an important regulator of schistosome-induced dermal inflammation (28). In this context, both T. ocellata and S. mansoni cercariae release similar types and quantities of eicosanoids (34), which are major factors in the regulation of IL-10 production by skin-derived cells (35).…”

Pivotal roles of the parasite PGD2 synthase and of the host D prostanoid receptor 1 in schistosome immune evasion

“…During murine schistosomiasis, parasite-derived eicosanoids may play important roles in the cutaneous immune response [15,28]. Immunolabeling with highly specific Ab indicated that Sm28GST is massively excreted in the epidermis of infected mice ( Fig.…”

Prostaglandin E2 Negatively Regulates the Production of Inflammatory Cytokines/Chemokines and IL-17 in Visceral Leishmaniasis

“…PGE 2 could be one such immunosuppressive molecule that has been found to be stimulated upon L. donovani infection (17). PGE 2 -dependent elevation of cAMP showed increased production of Th2 cytokine, IL-10, in mice (18,19). Apart from classical Th1 cytokine, Th17 cytokines have recently been reported for their protective role against visceral leishmaniasis (20).…”