Expression of major histocompatibility complex class II antigens and levels of interferon-gamma, tumour necrosis factor, and interleukin-6 in cerebrospinal fluid and serum in Toxoplasma gondii-infected SCID and immunocompetent C.B-17 mice.
In order to investigate activation of the innate immune system in murine toxoplasmosis, T- and B-cell-deficient SCID mice and their co-isogenic immunocompetent C.B-17 counterparts were orally infected with a low-virulent strain of Toxoplasma gondii (DX strain). SCID mice developed a fatal necrotizing toxoplasmosis, whereas CD4+ and CD8+ T cells contributing to inflammatory infiltrates conferred resistance to immunocompetent mice. Significant amounts of interferon-gamma (IFN-gamma) were detectable in SCID mice. The most likely source for this cytokine is activated natural killer (NK) cells. In comparison to immunocompetent mice IFN-gamma levels were reduced in cerebrospinal fluid (CSF) and serum of SCID mice at days 7 and 14 of disease. Similar amounts of tumour necrosis factor (TNF) were detected in both strains of mice. In addition, immunohistochemistry showed major histocompatibility complex (MHC) class II antigen expression on SCID and C.B-17 microglial cells and macrophages demonstrating activation of these cells in both strains. However, the up-regulation of MHC class II antigen on microglia was less pronounced in SCID mice, presumably due to reduced levels of IFN-gamma. Interleukin-6 (IL-6) levels in CSF and serum were elevated in both strains and correlated with systemic and intracerebral disease activity. In conclusion, our results demonstrate activation of macrophages and NK cells as the predominant defence mechanisms of the comprised SCID immune system during toxoplasma infection. This implies a major role for the innate immune system during early stages of toxoplasmosis although T cells are necessary to control the infection efficiently.
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Institut für Mikrobiologie und Hygiene, Klinikum der Stadt Mannheim, Fakultät für Klinische Medizin, Universität Heidelberg, Germany.
Deckert-Schlüter
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Schwendemann
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Brunner
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Hof
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D000818:Animals; D016207:Cytokines / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D016867:Immunocompromised Host / Q000276:immunology*; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D009206:Myocardium / Q000473:pathology; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma