Toll-like receptors 2 and 4 are necessary to generate a fully functional commensal-specific ocular immune response.

Abstract

Abstract Conjunctiva-associated lymphoid tissue (CALT) resembles a conventional mucosal immune tissue, which harbors various immune cells and is exposed to a wide array of microorganisms at the ocular surface. In a recent study, 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 dependent on IL-17 produced by gd T cells that respond to C. mast. In this study, we used mice deficient in the toll-like receptors, TLR2 and TLR4, to examine the role of these receptors in generating a gdT-17 immune response at the ocular surface. In vitro, we show that these receptors are necessary on dendritic cells (DCs) to effectively induce IL-17 production and proliferation of Vg4+ T cells. In vivo, we show that TLR2 KO mice and TLR4 KO mice fail to recruit Vg4+ T cells and neutrophils to the conjunctiva. These data suggest that both TLR2 and TLR4 are required to generate a fully functional mucosal IL-17 response in the conjunctiva and its draining lymph nodes. Our data highlight the importance of innate receptors in the generation of the ocular mucosal immune response and maintenance of gd T cell responses in vivo.