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- W2034117097 abstract "Abstract Background Tumour necrosis factor (TNF) α, lymphotoxin (LT) α, CD40L and FasL are members of the TNF family that play a crucial role in modulation of the immune response. Their role in the defence against infection with Candida albicans was investigated in mice deficient in either TNF-α and LT-α (TNF–/– LT–/– mice), CD40L (CD40L–/– mice) or Fas (MRL/lpr mice). Methods Mortality rates were compared in mice infected intravenously with 106 colony-forming units of C. albicans per mouse. Results After infection with C. albicans the TNF–/– LT–/– mice had a significantly increased mortality rate compared with control mice (100 versus 40 per cent; P < 0·01). This was due to a 10–1000-fold increased outgrowth of the yeasts in the kidneys and liver of TNF–/– LT–/– mice (P < 0·01). Defective recruitment and phagocytosis, but not Candida killing, were responsible for these effects. CD40L–/– mice were also more susceptible to systemic candidiasis than the wild-type controls (mortality rate 80 versus 50 per cent; P < 0·05), and the growth of Candida in the kidneys was one order of magnitude higher in the deficient than in control mice (P < 0·05). Neutrophil function in the CD40L–/– mice was normal, whereas decreased Candida killing by macrophages through nitric oxide-dependent mechanisms was responsible for the effect of CD40/CD40L interactions. In contrast, Fas-defective MRL/lpr mice were significantly more resistant to disseminated candidiasis (mortality rate 50 versus 100 per cent; P < 0·01); this was mediated by the facilitation of neutrophil migration to the site of infection. Conclusion Cytokines of the TNF family play a crucial role in the modulation of host defence against fatal C. albicans infection. Their effects are exerted selectively at the level of neutrophil or macrophage function." @default.
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- W2034117097 date "2000-07-01" @default.
- W2034117097 modified "2023-09-23" @default.
- W2034117097 title "Role of cytokines of the tumour necrosis factor family in the immune response to disseminated Candida albicans infection" @default.
- W2034117097 doi "https://doi.org/10.1046/j.1365-2168.2000.01544-24.x" @default.
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