Document Detail


A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells.
MedLine Citation:
PMID:  20833374     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
David L Moyes; Manohursingh Runglall; Celia Murciano; Chengguo Shen; Deepa Nayar; Selvam Thavaraj; Arinder Kohli; Ayesha Islam; Hector Mora-Montes; Stephen J Challacombe; Julian R Naglik
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell host & microbe     Volume:  8     ISSN:  1934-6069     ISO Abbreviation:  Cell Host Microbe     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-13     Completed Date:  2010-12-13     Revised Date:  2010-12-17    
Medline Journal Info:
Nlm Unique ID:  101302316     Medline TA:  Cell Host Microbe     Country:  United States    
Other Details:
Languages:  eng     Pagination:  225-35     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Oral Medicine, Pathology, and Immunology, King's College London Dental Institute, King's College London, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Candida albicans / cytology,  growth & development,  immunology*,  pathogenicity*
Candidiasis, Oral / immunology
Cell Line, Tumor
Cell Wall / immunology
Cytokines / metabolism
Dual Specificity Phosphatase 1 / metabolism
Epithelial Cells / immunology*,  metabolism,  microbiology*
Fungal Proteins / metabolism
Host-Pathogen Interactions
Humans
Hyphae / immunology
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinases / metabolism*
Mouth Mucosa / immunology*,  metabolism,  microbiology*
NF-kappa B / metabolism
Proto-Oncogene Proteins c-fos / metabolism
Signal Transduction
Virulence
Yeasts / metabolism
Grant Support
ID/Acronym/Agency:
080088//Wellcome Trust; DE017514/DE/NIDCR NIH HHS; R01 DE017514-05/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/Fungal Proteins; 0/NF-kappa B; 0/Proto-Oncogene Proteins c-fos; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.1.3.48/Dual Specificity Phosphatase 1
Comments/Corrections
Comment In:
Cell Host Microbe. 2010 Sep 16;8(3):219-20   [PMID:  20833371 ]
Nat Rev Immunol. 2010 Nov;10(11):752   [PMID:  21080615 ]

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