{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T10:45:44Z","timestamp":1766486744201,"version":"3.41.2"},"reference-count":84,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009156","name":"Nantong Science and Technology Bureau","doi-asserted-by":"publisher","award":["JC2021080","JC12022005"],"award-info":[{"award-number":["JC2021080","JC12022005"]}],"id":[{"id":"10.13039\/501100009156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Sepsis is characterized by an endotoxin tolerance phenotype that occurs in the stage of infection. Persistent bacterial infection can lead to immune cell exhaustion. Triad3A, an E3 ubiquitin ligase, negatively regulates its activation by TLR4. However, the effect of Triad3A on endotoxin tolerance and bactericidal ability in the state of endotoxin tolerance remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using single dose LPS and repeated LPS stimulated macrophage cell lines at indicated times, we investigated miR\u2010191, Tirad3A, TRAF3, TLR4, p\u2010P65, TNF\u2010\u03b1, IL\u20101\u03b2, and iNOS expression, the effect of miR\u2010191 on Triad3A and TRAF3, gene loss\u2010of\u2010function analyses, the effect of Triad3A on TLR4, p\u2010P65, cytokine, and mycobactericidal activity in endotoxin tolerant cells infected with <jats:italic>Mycobacterium marinum<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here we found that Triad3A is involved in regulating endotoxin tolerance. Our result also displayed that miR\u2010191 expression is downregulated in macrophages in the state of endotoxin tolerance. miR\u2010191 can directly bind to Triad3A and TRAF3. Additionally, knockdown of Triad3A can reverse the effect of decreasing TNF\u2010\u03b1 and IL\u20101\u03b2 in endotoxin tolerant macrophages. Furthermore, we demonstrated that the TLR4\u2010NF\u2010\u03baB\u2010NO pathway was associated with Triad3A and responsible for the killing of intracellular mycobacteria in a tuberculosis sepsis model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results provide new insight into the mechanisms of Triad3A induced tolerogenic phenotype in macrophages, which can help the better comprehension of the pathogenesis involved in septic shock with infection of <jats:italic>Mycobacterium<\/jats:italic>\u00a0<jats:italic>tuberculosis<\/jats:italic>, and suggest that Triad3A may be a potential drug target for the treatment of severe septic tuberculosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.925","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T04:19:50Z","timestamp":1690172390000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Triad3A involved in the regulation of endotoxin tolerance and mycobactericidal activity through the NF\u03baB\u2010nitric oxide pathway"],"prefix":"10.1002","volume":"11","author":[{"given":"Yongwei","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory The Sixth People's Hospital of Nantong Nantong Jiangsu China"},{"name":"Department of Pathogen Biology, School of Medicine Nantong University Nantong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinliang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine The Second Affiliated Hospital of Nantong University, Nantong First People's Hospital Nantong Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Medicine Nantong University Nantong 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