A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells.
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.
Moyes
David L
DL
Department of Oral Medicine, Pathology, and Immunology, King's College London Dental Institute, King's College London, London, UK.
Runglall
Manohursingh
M
Murciano
Celia
C
Shen
Chengguo
C
Nayar
Deepa
D
Thavaraj
Selvam
S
Kohli
Arinder
A
Islam
Ayesha
A
Mora-Montes
Hector
H
Challacombe
Stephen J
SJ
Naglik
Julian R
JR
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
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