title: Protection against epithelial damage during Candida albicans infection is mediated by PI3K/Akt and mammalian target of rapamycin signaling.
abstract: BACKGROUND
  The ability of epithelial cells (ECs) to discriminate between commensal and pathogenic microbes is essential for healthy living. Key to these interactions are mucosal epithelial responses to pathogen-induced damage.
  
  
  METHODS
  Using reconstituted oral epithelium, we assessed epithelial gene transcriptional responses to Candida albicans infection by microarray. Signal pathway activation was monitored by Western blotting and transcription factor enzyme-linked immunosorbent assay, and the role of these pathways in C. albicans-induced damage protection was determined using chemical inhibitors.
  
  
  RESULTS
  Transcript profiling demonstrated early upregulation of epithelial genes involved in immune responses. Many of these genes constituted components of signaling pathways, but only NF-κB, MAPK, and PI3K/Akt pathways were functionally activated. We demonstrate that PI3K/Akt signaling is independent of NF-κB and MAPK signaling and plays a key role in epithelial immune activation and damage protection via mammalian target of rapamycin (mTOR) activation.
  
  
  CONCLUSIONS
  PI3K/Akt/mTOR signaling may play a critical role in protecting epithelial cells from damage during mucosal fungal infections independent of NF-κB or MAPK signaling.
authors.affiliation: Department of Oral Immunology, King's College London Dental Institute.
authors.forename: David L
authors.initials: DL
authors.lastname: Moyes
authors.forename: Chengguo
authors.initials: C
authors.lastname: Shen
authors.forename: Celia
authors.initials: C
authors.lastname: Murciano
authors.forename: Manohursingh
authors.initials: M
authors.lastname: Runglall
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Richardson
authors.forename: Matthew
authors.initials: M
authors.lastname: Arno
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Aldecoa-Otalora
authors.forename: Julian R
authors.initials: JR
authors.lastname: Naglik
mesh_terms: D002176:Candida albicans / Q000502:physiology*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D025301:Hyphae; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D040081:Protein Array Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human
keywords: Akt; Candida albicans; MAPK; PI3 kinase; c-Fos; damage; epithelial; fungal; inflammation; mTOR; microarray