Microbiome-dependent modulation of mucosal immunity at the ocular surface.

Abstract

Abstract Mucosal sites that interface with the environment and provide barrier function include the intestine, nasopharynx, lung, female reproductive tract and the ocular surface. Disruption of immune homeostasis at the ocular surface is associated with discomfort, inflammation and potential loss of vision. Immune cells are present within the mucosa of the ocular surface (conjunctiva) and are affected by environmental factors, potentially including microorganisms. 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 address the question whether commensal microbes are present in ocular mucosa and modulate immunity. Our data indicate 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, conjunctival γδ T cells respond to a strain of Corynebacterium that colonizes the ocular surface by secreting IL-17, which modifies the inflammatory signature within the ocular mucosa. Furthermore, 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 infection. Our results indicate that a relationship exists between commensals and immune cells at the ocular surface, which is critical for maintenance of homeostasis and host defense within the ocular mucosa.