Abstract: Objective To investigate the role of Toll-like receptor 4 (TLR4) in the host defense against systemic candidiasis in murine model.Methods Two groups of mice,a study group (C3H/HeJ mice with mutant TLR4 gene) and a control group (C3H/HeN mice with normal TLR4 gene) were set up in cyclophosphamide-induced immuno-suppressed murine model with systemic candidiasis.Colony forming units (CFUs) of C.albicans were determined in infected kidneys and spleens with plating dilution method.Histopathological changes of infected kidneys were measured.In addition,levels of tumor necrosis factor-α (TNF-α) in kidneys were detected by enzyme-linked immunosorbent assay.Results CFUs of C.albicans were significantly higher in kidneys in the 1st day and 6th day after infection in the study group than those in the control group.Meanwhile,CFUs of C.albicans were significantly higher in spleens in the 1st day after infection in the study group than those in the control group.The scores of severity of infection,showed by histopathology,were significantly higher in kidneys in the 1st day and 6th day after infection in the study group than those in the control group(P<0.05).TNF-α concentrations were significantly lower in kidneys in the 1st day and 6th day after infection in the study group than those in the control group (P<0.05).Conclusion TLR4 may play a protective role in host defense against systemic candidiasis in murine model.

Key words: Toll-like receptor, Candidiasis, Animal testing alternatives