Toll-like Receptor 2/IL-1β signaling is required for sensing and responding to a commensal bacterium at the ocular surface

Abstract

Abstract Conjunctiva-associated lymphoid tissue (CALT) resembles a conventional mucosal immune tissue, and harbors a variety of immune cells. CALT is exposed to diverse microorganisms that come in contact with the ocular surface. Previously, we demonstrated that colonization of the ocular mucosa with the commensal bacterium, Corynebacterium mastitidis (C. mast), results in increased resistance of the ocular surface to infectious fungal and bacterial pathogens. Further, we showed that this effect is due to IL-17 produced by Vγ4+γδ T cells that respond to C. mast in an IL-1-dependent fashion. In this study, we show that the toll-like receptor 2 (TLR2) and IL-1β are important for IL-17 production, activation and proliferation of Vg4+ γδ T cells. Using in vivo and in vitro approaches, we show that cells of TLR2 KO mice have reduced production of IL-1β in response to C. mast. These mice also fail to recruit Vg4+γδ T cells and neutrophils to the conjunctiva. We interpret these data to mean that TLR2 is required for sensing this commensal on the conjunctiva and its draining lymph nodes to activate the inflammasome and consequent IL-1 production, which in turn drives the IL-17 response. Our data highlight the importance and the role of the innate receptor TLR2 in the generation of the ocular mucosal immune response and in maintenance of the homeostatic γδ T cell response at the ocular surface.