Toll-like receptor 4 defective mice carrying point or null mutations do not show increased susceptibility to Candida albicans in a model of hematogenously disseminated infection.
We have studied the role of TLR4 in murine defenses against Candida albicans in two TLR4-defective mouse strains: C3H/HeJ mice which have defective TLR4 signaling, and TLR4-/- knockout mice. Both TLR4-defective mice strains experimentally infected with virulent C. albicans cells showed no significant difference in survival as compared with their respective controls. Recruitment of neutrophils to the peritoneal cavity of i.p. infected mice was not affected in TLR4-/-animals, but significantly enhanced in C3H/HeJ mice, compared with their control mice. In vitro production of TNF-alpha by macrophages from both types of TLR4-defective mice, in response to yeasts and hyphae of C. albicans, was not diminished as compared with production by macrophages from wild-type mice. In vitro production of TNF-alpha by yeast-stimulated splenocytes from mice intravenously infected with the low-virulence C. albicans PCA2 strain was not affected in TLR4-defective mice, but the TNF-alpha production in response to hyphae was higher in TLR4-defective than in control animals; the production of IFN-gamma by these splenocytes was similar to controls, as well as the frequency of IFN-gamma-producing CD4+T lymphocytes, indicating that TLR4-defective mice are capable of mounting a Th1 adaptive immune response. Our data indicate that TLR4 is dispensable for murine immune resistance to C. albicans.
Murciano
C
C
Departamento de Microbiología y Ecología, Universitat de Valencia, Spain.
Villamon
E
E
Gozalbo
D
D
Roig
P
P
O'Connor
J E
JE
Gil
M L
ML
D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D017354:Point Mutation; D018417:Th1 Cells / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma