A role for parasite-induced PGE2 in IL-10-mediated host immunoregulation by skin stage schistosomula of Schistosoma mansoni.
Significant quantities of PGE(2) 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 PGE(2) production, suggesting that a different biochemical pathway may be involved in the production of PGE(2) by the parasite. In addition, the parasites were also able to induce PGE(2) 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 PGE(2) and IL-10 from keratinocytes. Further analysis of the parasite secretions showed that the PGE(2)/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 gamma-irradiation significantly abrogated their ability to induce PGE(2) 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 PGE(2) in IL-10-dependent down-regulation of host immune responses in the skin.
Ramaswamy
K
K
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL 61107, USA. ramswamy@uic.edu
Kumar
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D000818:Animals; D002474:Cell-Free System / Q000378:metabolism / Q000469:parasitology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D006131:Growth Inhibitors / Q000378:metabolism / Q000502:physiology; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000276:immunology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D007814:Larva / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012550:Schistosoma mansoni / Q000201:enzymology / Q000254:growth & development* / Q000276:immunology* / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D016861:Cyclooxygenase Inhibitors; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone