Interferon-gamma antagonizes transforming growth factor-beta2-mediated immunosuppression in murine Toxoplasma encephalitis.
The in vivo modulating activity of recombinant transforming growth factor (TGF)-beta2 on acute toxoplasmosis was evaluated in both Toxoplasma gondii susceptible C57BL/6 and resistant BALB/c mice. TGF-beta2 lethally exacerbated Toxoplasma encephalitis in C57BL/6, but not in BALB/c mice. In C57BL/6 mice, TGF-beta2 induced a profound dose-dependent increase of the intracerebral parasitic load as well as a reduction of IFN-gamma levels in serum and cerebrospinal fluid with a coincident decrease of MHC class II antigen expression of macrophages, microglial cells, and B cells. Furthermore, TGF-beta2-treated C57BL/6 mice showed a reduced activation of CD4+ and CD8+ T cells and a diminished recruitment of immune cells to the brain. The TGF-beta2-mediated development of lethal toxoplasmosis in C57BL/6 mice was abolished by treatment with recombinant interferon (IFN)-gamma.
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Institut für Med. Mikrobiologie und Hygiene, Klinikum Mannheim, Fakultät für Klinische Medizin der Universität Heidelberg, Germany.
Bertsch
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Frei
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Hübers
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Wiestler
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Hof
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Fontana
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Deckert-Schlüter
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D000818:Animals; D002452:Cell Count; D004198:Disease Susceptibility; D005260:Female; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology*; D016131:Lymphocyte Subsets / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors; D014122:Toxoplasma; D016781:Toxoplasmosis, Cerebral / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma