The Interleukin (IL) 17R/IL-22R Signaling Axis Is Dispensable for Vulvovaginal Candidiasis Regardless of Estrogen Status

J Infect Dis. 2020 Apr 7;221(9):1554-1563. doi: 10.1093/infdis/jiz649.

Abstract

Candida albicans, a ubiquitous commensal fungus that colonizes human mucosal tissues and skin, can become pathogenic, clinically manifesting most commonly as oropharyngeal candidiasis and vulvovaginal candidiasis (VVC). Studies in mice and humans convincingly show that T-helper 17 (Th17)/interleukin 17 (IL-17)-driven immunity is essential to control oral and dermal candidiasis. However, the role of the IL-17 pathway during VVC remains controversial, with conflicting reports from human data and mouse models. Like others, we observed induction of a strong IL-17-related gene signature in the vagina during estrogen-dependent murine VVC. As estrogen increases susceptibility to vaginal colonization and resulting immunopathology, we asked whether estrogen use in the standard VVC model masks a role for the Th17/IL-17 axis. We demonstrate that mice lacking IL-17RA, Act1, or interleukin 22 showed no evidence for altered VVC susceptibility or immunopathology, regardless of estrogen administration. Hence, these data support the emerging consensus that Th17/IL-17 axis signaling is dispensable for the immunopathogenesis of VVC.

Keywords: Candida albicans; IL-17; Th17; cytokines; fungal immunity; vaginitis; vulvovaginal candidiasis.

Publication types

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

MeSH terms

  • Animals
  • Candida albicans
  • Candidiasis, Oral / immunology
  • Candidiasis, Oral / pathology
  • Candidiasis, Vulvovaginal / immunology*
  • Candidiasis, Vulvovaginal / pathology
  • Disease Models, Animal
  • Estrogens / administration & dosage*
  • Estrogens / metabolism
  • Female
  • Interleukin-17 / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mucous Membrane / pathology
  • Receptors, Interleukin / immunology*
  • Receptors, Interleukin-17 / immunology*
  • Signal Transduction / immunology
  • Vagina / microbiology

Substances

  • Estrogens
  • Interleukin-17
  • Receptors, Interleukin
  • Receptors, Interleukin-17
  • interleukin-22 receptor