IL-22 neutralizing autoantibodies impair fungal clearance in murine oropharyngeal candidiasis model

Eur J Immunol. 2018 Mar;48(3):464-470. doi: 10.1002/eji.201747209. Epub 2017 Dec 11.

Abstract

Protection against mucocutaneous candidiasis depends on the T helper (Th)17 pathway, as gene defects affecting its integrity result in inability to clear Candida albicans infection on body surfaces. Moreover, autoantibodies neutralizing Th17 cytokines have been related to chronic candidiasis in a rare inherited disorder called autoimmune polyendocriopathy candidiasis ectodermal dystrophy (APECED) caused by mutations in autoimmune regulator (AIRE) gene. However, the direct pathogenicity of these autoantibodies has not yet been addressed. Here we show that the level of anti-IL17A autoantibodies that develop in aged Aire-deficient mice is not sufficient for conferring susceptibility to oropharyngeal candidiasis. However, patient-derived monoclonal antibodies that cross-react with murine IL-22 increase the fungal burden on C. albicans infected mucosa. Nevertheless, the lack of macroscopically evident infectious pathology on the oral mucosa of infected mice suggests that additional susceptibility factors are needed to precipitate a clinical disease.

Keywords: Aire; Cytokine autoantibodies; IL-22; Oropharyngeal candidiasis; Th17.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology*
  • Autoantibodies / immunology*
  • Candida albicans / immunology
  • Candidiasis, Chronic Mucocutaneous / immunology
  • Candidiasis, Chronic Mucocutaneous / microbiology
  • Candidiasis, Oral / immunology*
  • Candidiasis, Oral / microbiology*
  • Colony Count, Microbial
  • Cross Reactions
  • Disease Models, Animal
  • Disease Susceptibility
  • Female
  • Humans
  • Interleukin-17 / immunology
  • Interleukins / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Polyendocrinopathies, Autoimmune / immunology
  • Th17 Cells / immunology
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / immunology

Substances

  • APECED protein
  • Antibodies, Neutralizing
  • Autoantibodies
  • Interleukin-17
  • Interleukins
  • Transcription Factors
  • interleukin-22