Role of TLR1 and TLR6 in the host defense against disseminated candidiasis.
Toll-like receptor-1 (TLR1) and TLR6 are receptors of the TLR family that form heterodimers with TLR2. The role of TLR1 and TLR6 for the recognition of the fungal pathogen Candida albicans was investigated. TLR1 is not involved in the recognition of C. albicans, and TLR1 knock-out (TLR1-/-) mice showed a normal susceptibility to disseminated candidiasis. In contrast, recognition of C. albicans by TLR6 modulated the balance between Th1 and Th2 cytokines, and TLR6 knock-out mice displayed a defective production of IL-10 and an increased IFN-gamma release. Production of the monocyte-derived cytokines tumor necrosis factor, IL-1, and IL-6 was normal in TLR6-/- mice, and this was accompanied by a normal susceptibility to disseminated candidiasis. In conclusion, TLR6 is involved in the recognition of C. albicans and modulates the Th1/Th2 cytokine balance, but this results in a mild phenotype with a normal susceptibility of TLR6-/- mice to Candida infection.
Netea
Mihai G
MG
Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. m.netea@aig.umcn.nl
van de Veerdonk
Frank
F
Verschueren
Ineke
I
van der Meer
Jos W M
JW
Kullberg
Bart Jan
BJ
D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007668:Kidney / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016019:Survival Analysis; D051194:Toll-Like Receptor 1 / Q000172:deficiency / Q000276:immunology*; D051216:Toll-Like Receptor 6 / Q000172:deficiency / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D015850:Interleukin-6; C495369:Tlr6 protein, mouse; D051194:Toll-Like Receptor 1; D051216:Toll-Like Receptor 6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma