Toll-like receptors in ocular surface disease

Abstract

The ability of the ocular surface to mount an immune response is in part attributed to a family of proteins called toll-like receptors (TLRs). The latter are evolutionary conserved receptors that recognize and respond to various microbes and endogenous ligands. In addition to their recognition function, TLR activation triggers a complex signal transduction cascade that induces the production of inflammatory cytokines and co-stimulatory molecules, thus initiating innate and adaptive immunity. Toll-like receptor expression at the ocular surface is modulated during infection (e.g. Herpes simplex, bacterial keratitis and fungal keratitis) as well as during various inflammatory conditions (allergic conjunctivitis and dry eye syndrome). Here recent findings regarding TLR expression and their involvement in various ocular surface diseases are discussed.

Engagement of TLR2 Reverses the Suppressor Function of Conjunctiva CD4+CD25+Regulatory T Cells and Promotes Herpes Simplex Virus Epitope-Specific CD4+CD25−Effector T Cell Responses

“…[17][18][19] At least 13 TLRs that recognize a limited but conserved set of ligands from viral, bacterial, protozoan, and helminth pathogens have now been identified in mice and humans. 20 -23 It was initially thought that TLRs are primarily expressed by antigen-presenting cells (APCs) such as macrophages and dendritic cells and that interactions between microbial ligands and TLRs in these cells would indirectly result in the activation of effector T cells (T eff cells).…”

Toll-like receptors in domestic animals

“…The same applies to mononuclear cells. Several studies refer to expression of TLR members by ocular tissue (Pearlman et al 2010;Redfern and McDermott 2010). Although it is generally assumed that a high level of expression of a given TLR member indicates an efficient response to a PAMP, the study of expression is complicated by several factors: (1) it is not always clear whether nonexisting reports on certain TLR member expression means the virtual absence of a given TLR member from this tissue or organ, or a lack of relevant tools for analysis, or simply lacking information;…”

Toll-like receptors in ocular surface diseases: overview and new findings

“…Ueta et al [77] have shown polymorphisms in the TLR3 gene in patients with SJS (Stevens-Johnson syndrome) in a Japanese population and hypothesized that viral infection and/or drugs may trigger a disorder in the host innate immune response, leading to an abnormal inflammatory reaction of the mucosa, ocular surface and skin [8,13,19,77].…”

“…TLRs may be classified based on their localization (intracellular or surface) or by their ligands, which are highly conserved structures expressed by pathogens (not expressed by host cells), enabling the innate immune system to distinguish between self and nonself. Table 1 summarizes the common ligands recognized by TLRs and evidence for the expression of TLRs on corneal and conjunctival epithelia [7,12,18,19]. TLR2 mainly forms heterodimers with either TLR1 or TLR6 to recognize several bacterial products.…”