title: Identification of TLR10 as a key mediator of the inflammatory response to Listeria monocytogenes in intestinal epithelial cells and macrophages.
abstract: Listeria monocytogenes is a Gram-positive bacterium that can cause septicemia and meningitis. TLRs are central receptors of the innate immune system that drive inflammatory responses to invading microbes such as L. monocytogenes. Although intestinal epithelial cells (IECs) represent the initial point of entry used by L. monocytogenes for infection, the innate immune response to L. monocytogenes in these cells has been poorly characterized to date. The aim of this study was to determine which TLRs are involved in mediating the immune response to L. monocytogenes in IECs. We performed an RNA interference screen of TLRs 1-10 in the HT-29 IEC cell line and observed the most significant reduction in chemokine output following silencing of TLR10. This effect was also observed in the macrophage cell line THP-1. The chemokines CCL20, CCL1, and IL-8 were reduced following knockdown of TLR10. Silencing of TLR10 resulted in increased viability of L. monocytogenes in both HT-29 and THP-1 cells. TLR10 was found to be predominantly expressed intracellularly in epithelia, and activation required viable L. monocytogenes. NF-κB activation was seen to require TLR2 in addition to TLR10. Taken together, these data indicate novel roles for TLR10 in sensing pathogenic infection in both the epithelium and macrophages and have identified L. monocytogenes as a source of ligand for the orphan receptor TLR10.
authors.affiliation: Department of Pathology, University College Cork, National University of Ireland, Cork, Ireland;
authors.forename: Tim
authors.initials: T
authors.lastname: Regan
authors.forename: Ken
authors.initials: K
authors.lastname: Nally
authors.forename: Ruaidhri
authors.initials: R
authors.lastname: Carmody
authors.forename: Aileen
authors.initials: A
authors.lastname: Houston
authors.forename: Fergus
authors.initials: F
authors.lastname: Shanahan
authors.forename: John
authors.initials: J
authors.lastname: Macsharry
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Brint
mesh_terms: D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D005786:Gene Expression Regulation / Q000276:immunology; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D066298:In Vitro Techniques; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008024:Ligands; D008089:Listeria monocytogenes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D016328:NF-kappa B / Q000378:metabolism; D009928:Organ Specificity; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D051201:Toll-Like Receptor 10 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000502:physiology; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018925:Chemokines; D007378:Interleukins; D008024:Ligands; D016328:NF-kappa B; D034741:RNA, Small Interfering; C475955:TLR10 protein, human; C495342:TLR2 protein, human; D051201:Toll-Like Receptor 10; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors