title: Retinal Muller glia initiate innate response to infectious stimuli via toll-like receptor signaling.
abstract: Ocular surgeries and trauma predispose the eye to develop infectious endophthalmitis, which often leads to vision loss. The mechanisms of initiation of innate defense in this disease are not well understood but are presumed to involve retinal glial cells. We hypothesize that retinal Muller glia can recognize and respond to invading pathogens via TLRs, which are key regulators of the innate immune system. Using the mouse retinal sections, human retinal Muller cell line (MIO-M1), and primary mouse retinal Muller cells, we show that they express known human TLR1-10, adaptor molecules MyD88, TRIF, TRAM, and TRAF6, and co-receptors MD2 and CD14. Consistent with the gene expression, protein levels were also detected for the TLRs. Moreover, stimulation of the Muller glia with TLR 2, 3, 4, 5, 7 and 9 agonists resulted in an increased TLR expression as assayed by Western blot and flow cytometry. Furthermore, TLR agonists or live pathogen (S. aureus, P. aeruginosa, & C. albicans)-challenged Muller glia produced significantly higher levels of inflammatory mediators (TNF-α, IL-1β, IL-6 and IL-8), concomitantly with the activation of NF-κB, p38 and Erk signaling. This data suggests that Muller glia directly contributes to retinal innate defense by recognizing microbial patterns under infectious conditions; such as those in endophthalmitis.
authors.affiliation: Department of Ophthalmology, Kresge Eye Institute, Wayne State University, Detroit, Michigan, United States of America. akuma@med.wayne.edu
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: Nazeem
authors.initials: N
authors.lastname: Shamsuddin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007239:Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008024:Ligands; D020935:MAP Kinase Signaling System; D051379:Mice; D018448:Models, Immunological; D009457:Neuroglia / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology*; D012160:Retina / Q000473:pathology*; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D008024:Ligands; D051193:Toll-Like Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases