Trypanosoma cruzi: exposure of murine cells to live parasites in vitro leads to enhanced surface class I MHC expression which is type I interferon-dependent.
Previous reports indicate that myocardial cells from human patients with chronic Chagasic cardiomyopathy express increased levels of class I MHC molecules on their surfaces. To determine whether parasites can modulate class I expression, we have examined the effect of in vitro exposure to live Trypanosoma cruzi trypomastigotes on class I MHC expression by murine cells. Here we show that co-incubation of various murine cell lines, including 3T3 fibroblasts, J774.A1 macrophage-like cells, and freshly-explanted BALB/c primary embryo fibroblasts, with live trypomastigotes leads to a two- to fourfold increase in their expression of surface class I MHC molecules. Cell-free supernatants from T. cruzi-exposed cells, but not from either cells or parasites cultured alone, were also capable of upregulating class I expression, indicating the involvement of a soluble factor. Active supernatants were shown to contain IFN-alpha/beta activity and their ability to upregulate class I was inhibitable by anti-IFN-alpha/beta Abs. This ability of T. cruzi to enhance class I MHC expression on host cells via IFN-alpha/beta induction could be an important factor in the initiation of host immunity and/or immune-mediated pathology.
Department of Molecular Microbiology and Immunology, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
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Stryker
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Nickell
D000818:Animals; D001681:Biological Assay; D002450:Cell Communication; D002460:Cell Line; D005347:Fibroblasts / Q000276:immunology; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D007370:Interferon Type I / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014349:Trypanosoma cruzi / Q000276:immunology*; D015854:Up-Regulation
D015395:Histocompatibility Antigens Class I; D007370:Interferon Type I