Role of TLR5 in the Translocation and Dissemination of Commensal Bacteria in the Intestine after Traumatic Hemorrhagic Shock

• Published in: Journal of immunology research 2021, Vol.2021, p.6417658-21
• Main Authors: Zhang, Yun, Zhang, Jian, Xu, Tao, Zhang, Cheng, Yu, Wen-Qiao, Wei, Tao, Zhang, Bo, Chen, Qi, Qiu, Jun-Yu, Li, Hai-Jun, Liang, Ting-Bo
• Format: Article
• Language: English
• Subjects: Anaerobic bacteria; Animals; Antibodies; Bacteria; Bacterial infections; Bactericidal activity; Cell Differentiation; Cytokines; Dendritic cells; Dendritic Cells - immunology; Hemorrhage; Hemorrhagic shock; Homeostasis; Humans; Immune system; Immunity, Mucosal; Immunology; Infections; Intestinal microflora; Intestine; Intestines - immunology; Intestines - microbiology; Laboratory animals; Lamina propria; Lymphocyte Activation; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiota; Mucosal immunity; Mucous Membrane - pathology; Pathogens; Permeability; Polarization; Retinoic acid; Shock, Hemorrhagic - immunology; Shock, Hemorrhagic - microbiology; Software; Symbiosis; Th1 Cells - immunology; TLR5 protein; Toll-Like Receptor 5 - genetics; Toll-like receptors; Tretinoin - metabolism; Wounds and Injuries - immunology; Wounds and Injuries - microbiology
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2021/6417658

Enterogenous infection is a major cause of death during traumatic hemorrhagic shock (THS). It has been reported that Toll-like receptor 5 (TLR5) plays an integral role in regulating mucosal immunity and intestinal homeostasis of the microbiota. However, the roles played by TLR5 on intestinal barrier maintenance and commensal bacterial translocation post-THS are poorly understood. In this research, we established THS models in wild-type (WT) and Tlr5−/− (genetically deficient in TLR5 expression) mice. We found that THS promoted bacterial translocation, while TLR5 deficiency played a protective role in preventing commensal bacteria dissemination after THS. Furthermore, intestinal microbiota analysis uncovered that TLR5 deficiency enhanced the mucosal biological barrier by decreasing RegIIIγ-mediated bactericidal activity against G+ anaerobic bacteria. We then sorted small intestinal TLR5+ lamina propria dendritic cells (LPDCs) and analyzed TH1 differentiation in the intestinal lamina propria and a coculture system consisting of LPDCs and naïve T cells. Although TLR5 deficiency attenuated the regulation of TH1 polarization by LPDCs, it conferred stability to the cells during THS. Moreover, retinoic acid (RA) released from TLR5+ LPDCs could play a key role in modulating TH1 polarization. We also found that gavage administration of RA alleviated bacterial translocation in THS-treated WT mice. In summary, we documented that TLR5 signaling plays a pivotal role in regulating RegIIIγ-induced killing of G+ anaerobic bacteria, and LPDCs mediated TH1 differentiation via RA. These processes prevent intestinal bacterial translocation and enterogenous infection after THS, suggesting that therapeutically targeting LPDCs or gut microbiota can interfere with bacterial translocation after THS.