Pivotal roles of the parasite PGD2 synthase and of the host D prostanoid receptor 1 in schistosome immune evasion.
Prostaglandins (PG) are important modulators of immune and inflammatory responses. We recently demonstrated that the production of PGD(2) by the helminthic parasite Schistosoma mansoni inhibits the migration of epidermal Langerhans cells (LC) to the draining lymph nodes (DLN). Here, we identify the responsible parasite enzyme as being a 28-kDa glutathione-S-transferase (termed Sm28GST). Intradermal injection of Sm28GST in wild-type (WT), but not in D prostanoid receptor (DP) 1-deficient mice abrogates the departure of LC from the epidermis after TNF-alpha or FITC treatment. During infection, DP1 deficiency restores LC migration, but does not enhance the rate of T cell proliferation in the skin DLN. However, relative to WT mice, DLN cells from DP1-deficient infected mice produce dramatically less IFN-gamma and IL-10, but equal amount of IL-4. Interestingly, infected DP1-deficient mice develop a more Th2-biased humoral immune response, a significantly reduced parasitemia and a decreased egg-induced inflammatory response in the liver and intestines. Taken together, we propose that DP1 activation by the Sm28GST-derived PGD(2) could represent a strategy for the schistosome to evade host immune defenses. We also suggest that DP1 is important in the Th1/Th2 balance of the immune response and in inflammatory reactions during infection.
D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement; D005982:Glutathione Transferase / Q000502:physiology*; D015801:Helminth Proteins / Q000502:physiology*; D019746:Intramolecular Oxidoreductases / Q000502:physiology*; D007801:Langerhans Cells / Q000502:physiology; D054834:Lipocalins; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011982:Receptors, Prostaglandin / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000201:enzymology / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D015801:Helminth Proteins; D054834:Lipocalins; D011982:Receptors, Prostaglandin; D005982:Glutathione Transferase; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase