In vivo induction of neutrophil chemotaxis by secretory aspartyl proteinases of Candida albicans

Virulence. 2016 Oct 2;7(7):819-25. doi: 10.1080/21505594.2016.1184385. Epub 2016 Apr 29.

Abstract

Secretory aspartyl proteinases (Saps) of Candida albicans are key virulence traits which cause inflammasome-dependent, aseptic inflammation in a mouse model of vaginitis. In this paper, neutrophil migration in response to Sap2, Sap6 and chemo-attractive products released from Sap-treated vaginal epithelium was measured in vitro, ex vivo and in vivo. Our results show that Sap2 and Sap6 induce neutrophil migration and production of potent chemoattractive chemokines such as IL-8 and MIP-2 by vaginal epithelial cells. Our data suggest that at least part of MIP-2 production depends upon IL-1β activity. The vaginal fluid of Candida-infected mice contained a heat-labile inhibitor of neutrophil candidacidal activity that was absent from the vaginal fluid of Sap-treated mice. Overall, our data provide additional information on the capacity of C. albicans Saps to cause aseptic vaginal inflammation and highlight the potential role of some chemokines released from vaginal epithelial cells in this phenomenon.

Keywords: Candida albicans; aspartyl proteinases; killing activity; neutrophil migration; soluble factors.

MeSH terms

  • Animals
  • Aspartic Acid Endopeptidases / administration & dosage
  • Aspartic Acid Endopeptidases / metabolism*
  • Candida albicans / enzymology*
  • Candidiasis, Vulvovaginal / microbiology*
  • Chemokine CXCL2 / biosynthesis
  • Chemokine CXCL2 / immunology
  • Chemotaxis, Leukocyte*
  • Disease Models, Animal
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Epithelial Cells / microbiology
  • Female
  • Fungal Proteins / administration & dosage
  • Fungal Proteins / metabolism*
  • Humans
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / immunology
  • Mice
  • Neutrophils / physiology*
  • Vagina / chemistry
  • Vagina / cytology
  • Vagina / drug effects
  • Vagina / immunology

Substances

  • Chemokine CXCL2
  • Cxcl2 protein, mouse
  • Fungal Proteins
  • Interleukin-8
  • Aspartic Acid Endopeptidases
  • SAP2 protein, Candida
  • SAP6 protein, Candida albicans