June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Microbiome-dependent modulation of immunity at the ocular surface
Author Affiliations & Notes
  • Anthony J St. Leger
    Laboratory of Immunology, National Eye Institute, NIH, DERWOOD, Maryland, United States
  • Jigar Desai
    Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, United States
  • Rebecca Drummond
    Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, United States
  • Abirami Kugadas
    Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Fatimah Almaghrabi
    Laboratory of Immunology, National Eye Institute, NIH, DERWOOD, Maryland, United States
  • Phyllis Silver
    Laboratory of Immunology, National Eye Institute, NIH, DERWOOD, Maryland, United States
  • Mihaela Gadjeva
    Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Yoichiro Iwakura
    Center for Experimental Animal Models, Institute for Medical Sciences, Tokyo University of Science, Tokyo, Japan
  • Michail Lionakis
    Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, United States
  • Rachel R Caspi
    Laboratory of Immunology, National Eye Institute, NIH, DERWOOD, Maryland, United States
  • Footnotes
    Commercial Relationships   Anthony St. Leger, None; Jigar Desai, None; Rebecca Drummond, None; Abirami Kugadas, None; Fatimah Almaghrabi, None; Phyllis Silver, None; Mihaela Gadjeva, None; Yoichiro Iwakura, None; Michail Lionakis, None; Rachel Caspi, None
  • Footnotes
    Support  NIH Grants: EY025761, EY022054, Prevention of Blindness Society of Metropolitan Washington, American Association of Immunology Fellowship Award
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 842. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Anthony J St. Leger, Jigar Desai, Rebecca Drummond, Abirami Kugadas, Fatimah Almaghrabi, Phyllis Silver, Mihaela Gadjeva, Yoichiro Iwakura, Michail Lionakis, Rachel R Caspi; Microbiome-dependent modulation of immunity at the ocular surface. Invest. Ophthalmol. Vis. Sci. 2017;58(8):842.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Disruption of immune homeostasis at the ocular surface is associated with discomfort, inflammation and potential loss of vision. Immune cells are present within the conjunctiva and can be affected by environmental factors, potentially including microorganisms as seen in other classical mucosal sites like the intestine. However, proof that a resident ocular microbiome exists and influences local immunity has been elusive. We used a mouse model of ocular surface disease to study whether commensal microbes are present in ocular mucosa and modulate immunity.

Methods : Mice were either treated with PBS, topical antibiotics, or were ocularly inoculated with a Corynebacterium sp. that we show influences the immune signature within the conjunctiva. Tears were assessed for anti-microbial components and functionality. Conjunctivae were isolated and assessed for neutrophilic infiltration and IL- 17 production. We used an ocular model of Candida albicans to assess the functional implications of commensal bacteria colonization at the ocular surface.

Results : We found that IL-17 is constitutively produced within the conjunctiva-associated lymphoid tissue (CALT) and is necessary to recruit neutrophils to the ocular surface in the steady state and after a bacterial challenge. IL-17 sources in CALT include γδ T cells, αβ T cells and innate lymphoid cells (ILCs), in that order. Notably, a strain of Corynebacterium isolated from ocular tissue of mice, and known to also colonize the ocular mucosa of humans, induced the conjunctival γδ T cells to secrete IL-17, which modified the local inflammatory signature. We found that when this bacterium colonized the ocular mucosa it cannot be passed horizontally; however, it can be passed vertically from one generation to the next. This interaction appears necessary to regulate local immunity at the ocular surface, since elimination of these bacteria by antibiotic treatment, or their introduction into non-colonized mice, correlated inversely with severity of an experimental Candida albicans or Pseudomonas aeruginosa infection.

Conclusions : By satisfying all four of Koch's postulates, we have shown, for the first time, this Corynebacterium sp. directly induces a γδ/IL-17 driven protective immunity at the ocular surface. Thus showing that microbes can exist in ocular mucosa, are immunologically relevant, and can play a role in ocular disease.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×