{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:14:26Z","timestamp":1791000866981,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>TLRs are key sensors for conserved bacterial molecules and play a critical role in host defense against invading pathogens. Although the roles of TLRs in defense against pathogen infection and in maintaining gut immune homeostasis have been studied, the precise functions of different TLRs in response to pathogen infection in the gut remain elusive. The present study investigated the role of TLR signaling in defense against the Gram-negative bacterial pathogen Salmonella typhimurium. The results indicated that TLR9-deficient mice were more susceptible to S. typhimurium infection compared with wild-type and TLR2- or TLR4-deficient mice, as indicated by more severe intestinal damage and the highest bacterial load. TLR9 deficiency in intestinal epithelial cells (IECs) augmented the activation of NF-\u03baB and NLRP3 inflammasomes significantly, resulting in increased secretion of IL-1\u03b2. IL-1\u03b2 increased the expression of NKG2D on intestinal intraepithelial lymphocytes and NKG2D ligands on IECs, resulting in higher susceptibility of IECs to cytotoxicity of intestinal intraepithelial lymphocytes and damage to the epithelial barrier. We proposed that TLR9 regulates the NF-\u03baB\u2013NLRP3\u2013IL-1\u03b2 pathway negatively in Salmonella-induced NKG2D-mediated intestinal inflammation and plays a critical role in defense against S. typhimurium infection and in the protection of intestinal integrity.<\/jats:p>","DOI":"10.4049\/jimmunol.1601416","type":"journal-article","created":{"date-parts":[[2017,6,3]],"date-time":"2017-06-03T00:40:33Z","timestamp":1496450433000},"page":"761-773","source":"Crossref","is-referenced-by-count":73,"title":["TLR9 Regulates the NF-\u03baB\u2013NLRP3\u2013IL-1\u03b2 Pathway Negatively in <i>Salmonella<\/i>-Induced NKG2D-Mediated Intestinal Inflammation"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5609-1907","authenticated-orcid":false,"given":"Yan","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University , Jinan 250012,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meifang","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University , Jinan 250012,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengyan","family":"Zuo","sequence":"additional","affiliation":[{"name":"Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University , Jinan 250012,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University , Jinan 250012,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University , Jinan 250012,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Guan","sequence":"additional","affiliation":[{"name":"Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University , Jinan 250012,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renhui","family":"Zhan","sequence":"additional","affiliation":[{"name":"Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University , Jinan 250012,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuju","family":"Han","sequence":"additional","affiliation":[{"name":"Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University , Jinan 250012,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University , Jinan 250012,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3351-6420","authenticated-orcid":false,"given":"Rongbin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Immunology, School of Life Sciences, University of Science and Technology of China , Hefei 230027,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Immunology, School of Life Sciences, University of Science and Technology of China , Hefei 230027,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Tian","sequence":"additional","affiliation":[{"name":"Institute of Immunology, School of Life Sciences, University of Science and Technology of China , Hefei 230027,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3849-6676","authenticated-orcid":false,"given":"Cai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University , Jinan 250012,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,7,15]]},"reference":[{"key":"2025030614194466000_r1","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/cmi.2016.58","article-title":"Cellular and molecular regulation of innate inflammatory responses","volume":"13","author":"Liu","year":"2016","journal-title":"Cell. 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