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The Candida albicans toxin candidalysin mediates distinct epithelial inflammatory responses through p38 and EGFR-ERK

Spyridoula-Angeliki Nikou1,2, Chunsheng Zhou3, James S Griffiths2

  • 1Protein Phosphorylation Laboratory, Francis Crick Institute, London, UK.

Science Signaling
|April 5, 2022
PubMed

Insights

The fungal toxin candidalysin from Candida albicans activates distinct signaling pathways, including mitogen-activated protein kinase (MAPK) and epidermal growth factor receptor (EGFR), to drive inflammation and host defense during infection.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Candida albicans is a fungal pathogen that causes infections.
  • Candidalysin is a toxin secreted by C. albicans that damages host cells.
  • Epithelial cell damage triggers innate immune responses involving specific signaling pathways.

Purpose of the Study:

  • To investigate the signaling pathways activated by candidalysin in epithelial cells.
  • To determine the roles of MAPK and EGFR pathways in candidalysin-induced inflammation.
  • To elucidate the contribution of these pathways to host defense against C. albicans.

Main Methods:

  • Primary human oral epithelial cells were cultured.
  • Cells were treated with candidalysin.
  • Activation of MAPK (p38, ERK) and EGFR pathways was assessed.
  • Cytokine and chemokine release was measured.
  • Experiments were conducted in a mouse model of oral C. albicans infection.

Main Results:

  • Candidalysin activated p38 MAPK, leading to IL-6 release and EGFR phosphorylation.
  • p38 activation was independent of EGFR and involved MKKs and Src kinase.
  • Candidalysin also activated the EGFR-ERK pathway, inducing c-Fos and releasing neutrophil-activating chemokines.
  • Early clearance of C. albicans in mice required p38 but not c-Fos.

Conclusions:

  • Candidalysin differentially activates p38 and ERK pathways.
  • These pathways mediate distinct aspects of the innate immune response to C. albicans.
  • p38 signaling is crucial for early host defense against oral candidiasis.

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