IL-17-mediated antifungal defense in the oral mucosa is independent of neutrophils

Mucosal Immunol. 2015 Mar;8(2):221-31. doi: 10.1038/mi.2014.57. Epub 2014 Jul 9.

Abstract

Interleukin-17 (IL-17)-mediated immunity has emerged as a crucial host defense mechanism against Candida albicans infections in mucosal tissues and the skin. The precise mechanism by which the IL-17 pathway prevents fungal outgrowth has not been clarified. Neutrophils are critical for limiting fungal dissemination and IL-17 is generally thought to act by regulating neutrophil mobilization and trafficking to the site of infection. Using a mouse model of oropharyngeal candidiasis (OPC), we found that strikingly the IL-17 pathway is not required for the neutrophil response to C. albicans. Mice deficient for the IL-17 receptor subunits IL-17 receptor A (IL-17RA) or IL-17RC or mice depleted of IL-17A and IL-17F exhibited a normal granulocyte colony-stimulating factor (G-CSF) and CXC-chemokine response and displayed no defect in neutrophil recruitment or function. Instead, the inability of these mice to clear the fungus was associated with a selective defect in the induction of antimicrobial peptides (AMPs) in the epithelium that resulted in persistent fungal colonization. Importantly, this antifungal mechanism of IL-17A and IL-17F did not extend to the closely related family member IL-17C. Together, these data uncouple IL-17-dependent effector mechanisms from the neutrophil response and reveal a compartmentalization of the antifungal defense in the oral mucosa providing a new understanding of IL-17-mediated mucosal immunity against C. albicans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Candida albicans / immunology
  • Candidiasis, Oral / immunology
  • Candidiasis, Oral / metabolism
  • Candidiasis, Oral / microbiology
  • Disease Models, Animal
  • Fungi / immunology*
  • Immunophenotyping
  • Interleukin-17 / deficiency
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Mice
  • Mice, Knockout
  • Mouth Mucosa / immunology*
  • Mouth Mucosa / metabolism*
  • Mouth Mucosa / microbiology
  • Mouth Mucosa / pathology
  • Mycoses / immunology
  • Mycoses / metabolism
  • Mycoses / microbiology
  • Neutrophils / immunology*
  • Neutrophils / metabolism*
  • Neutrophils / microbiology
  • Phenotype
  • Signal Transduction

Substances

  • Interleukin-17