Candida albicans phospholipomannan is sensed through toll-like receptors.
Candida albicans is a common, harmless yeast in the human digestive tract that also causes severe systemic fungal infection in hospitalized patients. Its cell-wall surface displays a unique glycolipid called phospholipomannan (PLM). The ability of PLM to stimulate tumor necrosis factor (TNF)-alpha production by J774 mouse cells correlates with the activation of nuclear factor (NF)-kappaB. We examined the involvement of Toll-like receptors (TLRs) in PLM-dependent stimulation. Compared with wild-type cells, which produced large amounts of TNF-alpha after incubation with PLM, the deletion of the TLR4 and TLR6 genes led to a limited alteration of the PLM-induced response. Deletion of the TLR2 gene completely abolished the cell response. Surface expression of PLM is a phylogenic trait of C. albicans, and the recognition of PLM by TLRs, together with the unique pathogenic potential of C. albicans, suggests that this molecule may be a member of the pathogen-associated molecular pattern family.
Jouault
Thierry
T
Laboratoire de Mycologie Fondamentale et Appliquée, Inserm EMI0360, Université de Lille II, Lille, France. tjouault@univ-lille2.fr
Ibata-Ombetta
Stella
S
Takeuchi
Osamu
O
Trinel
Pierre-André
PA
Sacchetti
Paola
P
Lefebvre
Philippe
P
Akira
Shizuo
S
Poulain
Daniel
D
D000818:Animals; D002176:Candida albicans / Q000737:chemistry / Q000472:pathogenicity / Q000502:physiology*; D002460:Cell Line; D005260:Female; D006017:Glycolipids / Q000502:physiology*; D006801:Humans; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D006017:Glycolipids; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C400188:phospholipomannan