Lack of antigen-specific Th1 response alters granuloma formation and composition in Schistosoma mansoni-infected MyD88-/- mice.
To evaluate the role of the innate immune system during schistosomiasis in vivo, we infected myeloid differentiation factor 88 (MyD88)-deficient mice with Schistosoma mansoni and analyzed their pathognomonic formation of hepatic granulomas and T cell responses. Even though the differences between knockout and wild-type mice in terms of mortality, liver damage, serum IgE and parasite burden were insignificant, the liver granulomas in the MyD88-deficient mice were significantly smaller, less cellular and contained a reduced percentage of eosinophils. Histologically, these granulomas revealed stronger fibrosis, confirmed also by increased levels of soluble collagen and IL-13, implying a Th2 bias. Spleen cells from infected MyD88-deficient mice also produced significantly less IFN-gamma than their wild-type controls upon restimulation with Schistosoma-egg-antigen (SEA). Furthermore, SEA-loaded APC from naive wild-type or MyD88-deficient mice induced equal amounts of proliferation and cytokine secretion by T cells from wild-type infected mice. In contrast, Ag-specific T cells from infected MyD88-deficient mice produced hardly any IFN-gamma but considerably more IL-10, again regardless of the APC type. These findings indicate that the loss of IFN-gamma production is not due to impaired antigen presentation but may perhaps is due to suppression by IL-10-producing T cells. Thus, MyD88 plays an important role in cellular infiltration, granuloma composition and T cell responses during schistosomiasis.
Layland
Laura E
LE
Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.
Wagner
Hermann
H
da Costa
Clarissa U Prazeres
CU
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics*; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics*; D000947:Antigens, Helminth / Q000276:immunology*; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism; D004804:Eosinophils; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005355:Fibrosis; D006099:Granuloma / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000502:physiology; D018793:Interleukin-13 / Q000378:metabolism; D007958:Leukocyte Count; D008099:Liver / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D010063:Ovum / Q000276:immunology; D011971:Receptors, Immunologic / Q000172:deficiency* / Q000235:genetics*; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D000947:Antigens, Helminth; D018984:Epitopes, T-Lymphocyte; D018793:Interleukin-13; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic; D007073:Immunoglobulin E; D007371:Interferon-gamma; D003094:Collagen