Latorre E, Pradilla A, Chueca B, Pagán R, Layunta E, Alcalde A I, Mesonero J E
Departamento Farmacología y Fisiología, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain.
RNA-Mediated Mechanisms of Disease, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, UK.
Microb Ecol. 2016 Oct;72(3):730-9. doi: 10.1007/s00248-016-0809-6. Epub 2016 Aug 3.
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.
单核细胞增生李斯特菌是一种革兰氏阳性细菌,可引起严重感染。肠道微生物已被证明不仅通过免疫反应,还通过调节肠道血清素能系统对肠道生理功能产生影响。血清素(5-羟色胺,5-HT)是一种在肠道上皮细胞中合成的神经调节剂,可调节整个肠道生理功能。位于肠细胞中的血清素转运体(SERT)控制肠道5-HT的可用性,从而影响血清素的作用。单核细胞增生李斯特菌引起的感染通常被认为是由于其侵入肠道上皮细胞所致;然而,单核细胞增生李斯特菌对肠道上皮细胞的影响仍不清楚。因此,这项研究的主要目的是研究单核细胞增生李斯特菌对SERT的影响。使用Caco2/TC7细胞系作为类似肠细胞的体外模型,并进行了SERT功能和分子表达分析。我们的结果表明,活的单核细胞增生李斯特菌通过降低刷状缘膜上SERT的表达来抑制血清素摄取。然而,灭活的单核细胞增生李斯特菌和可溶性代谢产物均不能影响SERT。结果还表明,单核细胞增生李斯特菌可引起肠道上皮细胞中TLR2和TLR10转录变化,并提示TLR10可能参与了对SERT的抑制作用。因此,单核细胞增生李斯特菌可能通过TLR10介导的SERT抑制作用,诱导肠道血清素可用性增加,并可能导致肠道生理变化和炎症反应的启动。