Immunoregulatory effects triggered by immunobiotic Lactobacillus jensenii TL2937 strain involve efficient phagocytosis in porcine antigen presenting cells

Background: Immunobiotic Lactobacillus jensenii TL2937 modulates porcine mononuclear phagocytes from Peyer?s patches (PPMPs) and induces a differential production of pro- and anti-inflammatory cytokines in response to Toll-like receptor (TLR)-4 activation. Objective: In view of the important role played by phagocytosis in the activation of antigen presenting cells (APCs), the aim of the present work was to examine the interaction of TL2937 with porcine PPMPs focusing on phagocytosis. In addition, this study aimed to investigate whether the effects of L. jensenii TL2937 in porcine blood monocyte-derived dendritic cells (MoDCs) are similar to those found in PPMPs considering that MoDCs do not recapitulate all functions of mucosal APCs. Results: studies showed a high ability of porcine CD172a+ PPMPs to phagocytose L. jensenii TL2937. Interestingly, our results also revealed a reduced capacity of the non-immunomodulatory L. plantarum TL2766 to be phagocytosed by those immune cells. Phagocytosis of L. jensenii TL2937 by porcine PPMPs was partially dependent on TLR2. In addition, we demonstrated that TL2937 strain was able to improve the expression of IL-1, IL-12 and IL-10 in immature MoDCs resembling the effect of this immunobiotic bacterium on PPMPs. Moreover, similarly to PPMPs those immunomodulatory effects were related to the higher capacity of TL2937 to be phagocytosed by immature MoDCs. Conclusions: Microbial recognition in APCs could be effectively mediated through ligand-receptor interactions that then mediate phagocytosis and signaling. For the immunobiotic strain TL2937, TLR2 has a partial role for its interaction with porcine APCs and it is necessary to investigate the role of other receptors. A challenge for future research will be advance in the full understanding of the molecular interactions of immunobiotic L. jensenii TL2937 with porcine APCs that will be crucial for the successful development of functional feeds for the porcine host. This study is a step in that direction.Fil: Tsukida, Kohichiro. Tohoku University; JapónFil: Takahashi, Takuya. Tohoku University; JapónFil: Iida, Hikaru. Tohoku University; JapónFil: Kanmani, Paulraj. Tohoku University; JapónFil: Suda, Yoshihito. Miyagi University; JapónFil: Nochi, Tomonori. Tohoku University; JapónFil: Ohwada, Shuichi. Tohoku University; JapónFil: Aso, Hisashi. Tohoku University; JapónFil: Ohkawara, Sou. Meiji Seika Pharma Co., Ltd. Agricultural & Veterinary Division; JapónFil: Makino, Seiya. Meiji Co., Ltd. Division of Research and Development; JapónFil: Kano, Hiroshi. Meiji Co., Ltd. Division of Research and Development; JapónFil: Saito, Tadao. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Kitazawa, Haruki. Tohoku University; Japó

Immunobiotic Lactobacillus jensenii modulates toll-like receptor 4-induced inflammatory response via negative regulation in porcine antigen presenting cells

Previously, we demonstrated that Lactobacillus (L.) jensenii TL2937 attenuates the inflammatory response triggered by activation of toll-like receptor (TLR)-4 in porcine intestinal epithelial cells. In view of the critical importance of antigen-presenting cells (APCs) polarization in immunoregulation, the objective of the present study was to examine the effect of TL2937 strain on activation patterns of APCs from swine Peyer's patches (PPs). We demonstrated that direct exposure of porcine APCs to L. jensenii in the absence of inflammatory signals increased expression of IL-10 and TGF-β in CD172a+ APCs and caused them to display tolerogenic properties. In addition, pre-treatment of CD172a+ APCs with L. jensenii resulted in differential modulation of the production of pro- and anti-inflammatory cytokines in response to TLR4 activation. The immunomodulatory effect of TL2937 strain was not related to a downregulation of TLR4 but an upregulation of the expression of three negative regulators of TLRs: SIGIRR, A20, and IRAK-M. Our results also indicated that TLR2 has an important role in the anti-inflammatory activity of L. jensenii TL2937 since anti-TLR2 antibodies blocked the upregulation of SIGIRR and IRAK-M in CD172a+ APCs and the production of IL-10 in response to TLR4 activation. We performed, for the first time, a precise functional characterization of porcine APCs from PPs, and we demonstrated that CD172a+ cells were tolerogenic. Our findings demonstrate that adherent cells and isolated CD172a+ cells harvested from swine PPs were useful for in vitro study of the inflammatory responses in the porcine gut and the immunomodulatory effects of immunobiotic microorganisms.Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Tohuku University. Graduate School of Agricultural Science. Food Immunology Group; JapónFil: Suzuki, Rie. Tohuku University. Graduate School of Agricultural Science. Food Immunology Group; JapónFil: Fujie, Hitomi. Tohuku University. Graduate School of Agricultural Science. Food Immunology Group; JapónFil: Chiba, Eriko. Tohuku University. Graduate School of Agricultural Science. Food Immunology Group; JapónFil: Takahashi, Takuya. Tohuku University. Graduate School of Agricultural Science. Food Immunology Group; JapónFil: Tomosada, Yohsuke. Tohuku University. Graduate School of Agricultural Science. Food Immunology Group; JapónFil: Shimazu, Tomoyuki. Tohuku University. Graduate School of Agricultural Science. Food Immunology Group; JapónFil: Aso, Hisashi. Tohoku University. Graduate School of Agricultural Science. Cell Biology Laboratory; JapónFil: Ohwada, Shuichi. Tohoku University. Graduate School of Agricultural Science. Cell Biology Laboratory; JapónFil: Suda, Yoshihito. Miyagi University. Department of Food, Agriculture and Environmental Science; JapónFil: Ikegami, Shuji. Meiji Dairies Corporation. Division of Research and Development; JapónFil: Itoh, Hiroyuki. Meiji Dairies Corporation. Division of Research and Development; JapónFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Saito, Tadao. Tohuku University. Graduate School of Agricultural Science. Food Immunology Group; JapónFil: Kitazawa, Haruki. Tohuku University. Graduate School of Agricultural Science. Food Immunology Group; Japó