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