Protection against epithelial damage during Candida albicans infection is mediated by PI3K/Akt and mammalian target of rapamycin signaling

J Infect Dis. 2014 Jun 1;209(11):1816-26. doi: 10.1093/infdis/jit824. Epub 2013 Dec 19.

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.

Keywords: Akt; Candida albicans; MAPK; PI3 kinase; c-Fos; damage; epithelial; fungal; inflammation; mTOR; microarray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida albicans / physiology*
  • Cell Line, Tumor
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology*
  • Gene Expression Regulation / immunology
  • Humans
  • Hyphae
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Array Analysis
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / immunology
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Transcriptome

Substances

  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt