Tolerization of Mice to Schistosoma mansoni Egg Antigens Causes Elevated Type 1 and Diminished Type 2 Cytokine Responses and Increased Mortality in Acute Infection

作者: Padraic G. Fallon , David W. Dunne

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摘要: The granuloma that surrounds the Schistosoma mansoni egg is cause of pathology in murine schistosomiasis, and its formation driven by Ag-stimulated type 1 2 cytokines. To determine role egg-driven immune responses during schistosome infection we rendered CBA/Ca mice unresponsive to eggs combined cyclophosphamide treatment thymectomy. In early acute stages infection, egg-tolerized suffered high mortalities. Granuloma size deposition collagen liver were significantly reduced mice. Similarly, limited detected intestines these mice, this was associated with a >90% reduction excretion. Histologically, had exacerbated hepatocyte damage, extensive microvesicular steatosis. Elevated plasma transaminase levels confirmed damage hepatocytes. Infected impaired proliferation Ag but intact worm Ag. Tolerized diminished Ab cytokine isotype pattern Ag, elevated IgG2a IgG1 IgE. Egg-tolerized failed down-regulate cytokines are normally elicited infection. Hepatic cells from also dominated, frequencies Tc1/Th1 Tc2/Th2 cells. This study demonstrates tolerized have anti-egg effects detrimental host.

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