Background: Toll-like Receptor 9 (TLR9) is expressed mainly in the endosomal membrane of intestinal cells and mediates intestinal host-microbiota interaction. Serotonin (5-HT) is an intestinal neuromodulator involved in the intestinal immunity and homeostasis. In addition, a high level of 5-HT has been described in intestinal inflammation. 5-HT intestinal availability is mainly regulated by the serotonin transporter (SERT) expressed in enterocytes. Aim: The interaction of TLR9 with serotoninergic system remains known. Therefore, the aim of the present study was to assess the effects of TLR9 activation on SERT activity and expression. Methods: Caco-2 cells and colon from wild type (WT) and TLR9 C57BL/10 mice were used in this study. SERT activity (5-HT uptake) in Caco-2 cells and SERT expression (RT-qPCR and western blotting) in both Caco-2 cells and colon from WT and TLR9 mice, were analyzed. TLR9 mRNA and protein levels were also measured in Caco-2 cells. Results: TLR9 activation in Caco-2 cells reduced SERT activity in a MyD88 independent-way. SERT mRNA and protein level in both cell lysate and brush border membrane, were also diminished. SERT protein expression in colon of TLR9 mice resulted augmented compared with WT mice. Interestingly, activation of TLR9 in Caco-2 cells diminished TLR9 mRNA and protein in the cell lysate; however, TLR9 protein in brush border resulted increased. Conclusions: The results of this work highlight the role of TLR9 as a mediator intestinal homeostasis and/or intestinal inflammation by regulating intestinal serotoninergic system
