title: Listeria monocytogenes Inhibits Serotonin Transporter in Human Intestinal Caco-2 Cells.
abstract: Listeria monocytogenes is a Gram-positive bacterium that can cause a serious infection. Intestinal microorganisms have been demonstrated to contribute to intestinal physiology not only through immunological responses but also by modulating the intestinal serotonergic system. Serotonin (5-HT) is a neuromodulator that is synthesized in the intestinal epithelium and regulates the whole intestinal physiology. The serotonin transporter (SERT), located in enterocytes, controls intestinal 5-HT availability and therefore serotonin's effects. Infections caused by L. monocytogenes are well described as being due to the invasion of intestinal epithelial cells; however, the effect of L. monocytogenes on the intestinal epithelium remains unknown. The main aim of this work, therefore, was to study the effect of L. monocytogenes on SERT. Caco2/TC7 cell line was used as an enterocyte-like in vitro model, and SERT functional and molecular expression assays were performed. Our results demonstrate that living L. monocytogenes inhibits serotonin uptake by reducing SERT expression at the brush border membrane. However, neither inactivated L. monocytogenes nor soluble metabolites were able to affect SERT. The results also demonstrate that L. monocytogenes yields TLR2 and TLR10 transcriptional changes in intestinal epithelial cells and suggest that TLR10 is potentially involved in the inhibitory effect observed on SERT. Therefore, L. monocytogenes, through TLR10-mediated SERT inhibition, may induce increased intestinal serotonin availability and potentially contributing to intestinal physiological changes and the initiation of the inflammatory response.
authors.affiliation: Departamento Farmacología y Fisiología, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain. e.latorre@exeter.ac.uk.|RNA-Mediated Mechanisms of Disease, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, UK. e.latorre@exeter.ac.uk.
authors.forename: E
authors.identifier: 0000-0002-5797-3909
authors.initials: E
authors.lastname: Latorre
authors.affiliation: Departamento Farmacología y Fisiología, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Pradilla
authors.affiliation: Departamento de Producción Animal y Ciencia de los Alimentos, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain.|Instituto Agroalimentario de Aragón - IA2, Universidad de Zaragoza - CITA, Zaragoza, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Chueca
authors.affiliation: Departamento de Producción Animal y Ciencia de los Alimentos, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain.|Instituto Agroalimentario de Aragón - IA2, Universidad de Zaragoza - CITA, Zaragoza, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Pagán
authors.affiliation: Departamento Farmacología y Fisiología, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain.|Instituto Agroalimentario de Aragón - IA2, Universidad de Zaragoza - CITA, Zaragoza, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Layunta
authors.affiliation: Departamento Farmacología y Fisiología, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain.|Instituto Agroalimentario de Aragón - IA2, Universidad de Zaragoza - CITA, Zaragoza, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Alcalde
authors.affiliation: Departamento Farmacología y Fisiología, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain.|Instituto Agroalimentario de Aragón - IA2, Universidad de Zaragoza - CITA, Zaragoza, Spain.
authors.forename: J E
authors.initials: JE
authors.lastname: Mesonero
mesh_terms: D018938:Caco-2 Cells / Q000187:drug effects*; D018929:Cell Culture Techniques; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*; D008089:Listeria monocytogenes / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D008088:Listeriosis; D008828:Microbiological Techniques; D053594:Myeloid Differentiation Factor 88; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000096:biosynthesis / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000037:antagonists & inhibitors*; D051201:Toll-Like Receptor 10 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: D053594:Myeloid Differentiation Factor 88; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D051201:Toll-Like Receptor 10; D051195:Toll-Like Receptor 2; C507779:MYD88 protein, human; C475955:TLR10 protein, human; C495342:TLR2 protein, human
keywords: 5-HT; Intestinal epithelium; Listeriosis; SERT; TLR