title: Retinal photoreceptor expresses toll-like receptors (TLRs) and elicits innate responses following TLR ligand and bacterial challenge.
abstract: Toll-like receptors (TLRs) play an important role in host defense against microbial pathogens. Our previous studies have shown that TLRs are expressed on various retinal cells (Microglia and Müller glia) and orchestrate retinal innate responses in bacterial endophthalmitis. In this study, we used a well-characterized mouse cone photoreceptor cell line (661W); and demonstrated that these cells express all known TLRs. Although the stimulation of 661W cells with TLR ligands (Pam3Cys, PolyI:C, LPS, Flagellin, Poly DT, and ODN) did not alter TLR expression, downstream TLR-signaling pathways (NF-κB, p38, and ERK) are activated. Moreover, TLR-activated 661W cells secreted significant amounts of inflammatory mediators (IL-6, IL-1β, MIP-2, and KC) in their culture supernatant, as assessed by ELISA. A similar trend was observed in 661W cells challenged with live bacteria (Staphylococcus aureus). Interestingly, the neutralization of TLR2, a major receptor for S. aureus recognition, did not significantly attenuate bacterial-induced inflammatory mediators, suggesting the existence of TLR2-independent mechanisms in photoreceptor cells. Together, these results indicate that photoreceptors constitutively express functional TLRs and possess the ability to initiate innate responses following pathogen challenge, implicating their role in retinal innate immunity.
authors.affiliation: Kresge Eye Institute, Wayne State University School of Medicine, Detroit, Michigan, United States of America; Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Pawan Kumar
authors.initials: PK
authors.lastname: Singh
authors.affiliation: Kresge Eye Institute, Wayne State University School of Medicine, Detroit, Michigan, United States of America; Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007113:Immunity, Innate / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008024:Ligands; D020935:MAP Kinase Signaling System / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000382:microbiology; D016328:NF-kappa B / Q000276:immunology; D020419:Photoreceptor Cells, Vertebrate / Q000276:immunology* / Q000382:microbiology; D012160:Retina / Q000276:immunology* / Q000382:microbiology; D015398:Signal Transduction / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008024:Ligands; D016328:NF-kappa B; D051193:Toll-Like Receptors; D048051:p38 Mitogen-Activated Protein Kinases