title: Candida albicans phospholipomannan triggers inflammatory responses of human keratinocytes through Toll-like receptor 2.
abstract: The Toll-like receptors (TLRs) play an important role in the recognition of Candida albicans components and activation of innate immunity. Phospholipomannan (PLM), a glycolipid, is expressed at the surface of C. albicans cell wall, which acts as a member of the pathogen-associated molecular patterns family. In this study, we sought to clarify whether C. albicans-native PLM could induce an inflammation response in human keratinocytes and to determine the underlying mechanisms. Exposure of cultured human primary keratinocytes to PLM led to the increased gene expression and secretion of proinflammatory cytokines (IL-6) and chemokines (IL-8). PLM hydrolysed with beta-d-mannoside mannohydrolase failed to induce gene expression and secretion of IL-6 and IL-8. PLM up-regulated the mRNA and protein levels of TLR2, whereas the mRNA level of TLR4 was not altered. Keratinocytes challenged with PLM resulted in the activation of NF-kappaB and mitogen-activated protein kinase (MAPKs) including p38. Anti-TLR2 neutralizing antibody, NFkappaB and p38MAPK inhibitors blocked the PLM-induced secretion of IL-6, IL-8 in keratinocytes, but no such effect was observed in pretreatment with anti-TLR4-neutralizing antibody and lipopolysaccharide inhibitor (polymyxin B). These data suggest C. albicans-native PLM may contribute to the inflammatory responses of cutaneous candidiasis in the TLR2-NF-kappaB and p38MAPK signalling pathway dependent manner.
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Science & Peking Union Medical College, 12 Jiangwangmiao St., Nanjing 210042, China. minli08@gmail.com
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.forename: Yongnian
authors.initials: Y
authors.lastname: Shen
authors.forename: Weida
authors.initials: W
authors.lastname: Liu
mesh_terms: D002176:Candida albicans / Q000378:metabolism; D002179:Candidiasis, Cutaneous / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006017:Glycolipids / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D006017:Glycolipids; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C400188:phospholipomannan; D048051:p38 Mitogen-Activated Protein Kinases