title: A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells.
abstract: Discriminating between commensal and pathogenic states of opportunistic pathogens is critical for host mucosal defense and homeostasis. The opportunistic human fungal pathogen Candida albicans is also a constituent of the normal oral flora and grows either as yeasts or hyphae. We demonstrate that oral epithelial cells orchestrate an innate response to C. albicans via NF-κB and a biphasic MAPK response. Activation of NF-κB and the first MAPK phase, constituting c-Jun activation, is independent of morphology and due to fungal cell wall recognition. Activation of the second MAPK phase, constituting MKP1 and c-Fos activation, is dependent upon hypha formation and fungal burdens and correlates with proinflammatory responses. Such biphasic response may allow epithelial tissues to remain quiescent under low fungal burdens while responding specifically and strongly to damage-inducing hyphae when burdens increase. MAPK/MKP1/c-Fos activation may represent a "danger response" pathway that is critical for identifying and responding to the pathogenic switch of commensal microbes.
authors.affiliation: Department of Oral Medicine, Pathology, and Immunology, King's College London Dental Institute, King's College London, London, UK.
authors.forename: David L
authors.initials: DL
authors.lastname: Moyes
authors.forename: Manohursingh
authors.initials: M
authors.lastname: Runglall
authors.forename: Celia
authors.initials: C
authors.lastname: Murciano
authors.forename: Chengguo
authors.initials: C
authors.lastname: Shen
authors.forename: Deepa
authors.initials: D
authors.lastname: Nayar
authors.forename: Selvam
authors.initials: S
authors.lastname: Thavaraj
authors.forename: Arinder
authors.initials: A
authors.lastname: Kohli
authors.forename: Ayesha
authors.initials: A
authors.lastname: Islam
authors.forename: Hector
authors.initials: H
authors.lastname: Mora-Montes
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Challacombe
authors.forename: Julian R
authors.initials: JR
authors.lastname: Naglik
mesh_terms: D002176:Candida albicans / Q000166:cytology / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity*; D002180:Candidiasis, Oral / Q000276:immunology; D045744:Cell Line, Tumor; D002473:Cell Wall / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D005656:Fungal Proteins / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D025301:Hyphae / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009061:Mouth Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D016328:NF-kappa B / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D015398:Signal Transduction; D014774:Virulence; D015003:Yeasts / Q000378:metabolism
chemical_list: D016207:Cytokines; D005656:Fungal Proteins; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1