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

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...

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Autores principales: Yun Zhang, Jian Zhang, Tao Xu, Cheng Zhang, Wen-Qiao Yu, Tao Wei, Bo Zhang, Qi Chen, Jun-Yu Qiu, Hai-Jun Li, Ting-Bo Liang
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Publicado: Hindawi Limited 2021
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spelling oai:doaj.org-article:0c448ddbcdab4d2790fec8bf82e9bddf2021-11-29T00:55:53ZRole of TLR5 in the Translocation and Dissemination of Commensal Bacteria in the Intestine after Traumatic Hemorrhagic Shock2314-715610.1155/2021/6417658https://doaj.org/article/0c448ddbcdab4d2790fec8bf82e9bddf2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/6417658https://doaj.org/toc/2314-7156Enterogenous 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.Yun ZhangJian ZhangTao XuCheng ZhangWen-Qiao YuTao WeiBo ZhangQi ChenJun-Yu QiuHai-Jun LiTing-Bo LiangHindawi LimitedarticleImmunologic diseases. AllergyRC581-607ENJournal of Immunology Research, Vol 2021 (2021)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
spellingShingle Immunologic diseases. Allergy
RC581-607
Yun Zhang
Jian Zhang
Tao Xu
Cheng Zhang
Wen-Qiao Yu
Tao Wei
Bo Zhang
Qi Chen
Jun-Yu Qiu
Hai-Jun Li
Ting-Bo Liang
Role of TLR5 in the Translocation and Dissemination of Commensal Bacteria in the Intestine after Traumatic Hemorrhagic Shock
description 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.
format article
author Yun Zhang
Jian Zhang
Tao Xu
Cheng Zhang
Wen-Qiao Yu
Tao Wei
Bo Zhang
Qi Chen
Jun-Yu Qiu
Hai-Jun Li
Ting-Bo Liang
author_facet Yun Zhang
Jian Zhang
Tao Xu
Cheng Zhang
Wen-Qiao Yu
Tao Wei
Bo Zhang
Qi Chen
Jun-Yu Qiu
Hai-Jun Li
Ting-Bo Liang
author_sort Yun Zhang
title Role of TLR5 in the Translocation and Dissemination of Commensal Bacteria in the Intestine after Traumatic Hemorrhagic Shock
title_short Role of TLR5 in the Translocation and Dissemination of Commensal Bacteria in the Intestine after Traumatic Hemorrhagic Shock
title_full Role of TLR5 in the Translocation and Dissemination of Commensal Bacteria in the Intestine after Traumatic Hemorrhagic Shock
title_fullStr Role of TLR5 in the Translocation and Dissemination of Commensal Bacteria in the Intestine after Traumatic Hemorrhagic Shock
title_full_unstemmed Role of TLR5 in the Translocation and Dissemination of Commensal Bacteria in the Intestine after Traumatic Hemorrhagic Shock
title_sort role of tlr5 in the translocation and dissemination of commensal bacteria in the intestine after traumatic hemorrhagic shock
publisher Hindawi Limited
publishDate 2021
url https://doaj.org/article/0c448ddbcdab4d2790fec8bf82e9bddf
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