An Ocular Commensal Protects against Corneal Infection by Driving an Interleukin-17 Response from Mucosal γδ T Cells

Immunity. 2017 Jul 18;47(1):148-158.e5. doi: 10.1016/j.immuni.2017.06.014. Epub 2017 Jul 11.

Abstract

Mucosal sites such as the intestine, oral cavity, nasopharynx, and vagina all have associated commensal flora. The surface of the eye is also a mucosal site, but proof of a living, resident ocular microbiome remains elusive. Here, we used a mouse model of ocular surface disease to reveal that commensals were present in the ocular mucosa and had functional immunological consequences. We isolated one such candidate commensal, Corynebacterium mastitidis, and showed that this organism elicited a commensal-specific interleukin-17 response from γδ T cells in the ocular mucosa that was central to local immunity. The commensal-specific response drove neutrophil recruitment and the release of antimicrobials into the tears and protected the eye from pathogenic Candida albicans or Pseudomonas aeruginosa infection. Our findings provide direct evidence that a resident commensal microbiome exists on the ocular surface and identify the cellular mechanisms underlying its effects on ocular immune homeostasis and host defense.

Keywords: IL-17; host defense; microbiome; mucosal immunity; ocular commensal bacteria; ocular surface disease; γδ T cells.

MeSH terms

  • Animals
  • Candida albicans / immunology*
  • Candidiasis / immunology*
  • Candidiasis / microbiology
  • Cornea / immunology*
  • Cornea / microbiology
  • Corynebacterium / immunology*
  • Corynebacterium Infections / immunology*
  • Corynebacterium Infections / microbiology
  • Disease Models, Animal
  • Eye Infections / immunology*
  • Eye Infections / microbiology
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Mucosal*
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbiota / immunology*
  • Neutrophil Infiltration
  • Neutrophils / immunology*
  • Neutrophils / microbiology
  • Pseudomonas Infections / immunology*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • T-Lymphocytes / immunology*
  • Tears / immunology*

Substances

  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta