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Microbiol."],"abstract":"<jats:p><jats:italic>Helicobacter pylori<\/jats:italic> (<jats:italic>H. pylori<\/jats:italic>) is one of the gram-negative bacteria that mainly colonize the stomach mucosa and cause many gastrointestinal diseases, such as gastritis, peptic ulcer, and gastric cancer. Macrophages play a key role in eradicating <jats:italic>H. pylori<\/jats:italic>. Recent data have shown that Notch signaling could modulate the activation and bactericidal activities of macrophages. However, the role of Notch signaling in macrophages against <jats:italic>H. pylori<\/jats:italic> remains unclear. In the present study, in the co-culture model of macrophages with <jats:italic>H. pylori<\/jats:italic>, the inhibition of Notch signaling using \u03b3-secretase decreased the expression of inducible nitric oxide synthase (iNOS) and its product, nitric oxide (NO), and downregulated the secretion of pro-inflammatory cytokine and attenuated phagocytosis and bactericidal activities of macrophages to <jats:italic>H. pylori<\/jats:italic>. Furthermore, we identified that Jagged1, one of Notch signaling ligands, was both upregulated in mRNA and protein level in activated macrophages induced by <jats:italic>H. pylori<\/jats:italic>. Clinical specimens showed that the number of Jagged1<jats:sup>+<\/jats:sup> macrophages in the stomach mucosa from <jats:italic>H. pylori<\/jats:italic>-infected patients was significantly higher than that in healthy control. The overexpression of Jagged1 promoted bactericidal activities of macrophages against <jats:italic>H. pylori<\/jats:italic> and siRNA-Jagged1 presented the opposite effect. Besides, the addition of exogenous rJagged1 facilitated the pro-inflammatory mediators of macrophages against <jats:italic>H. pylori<\/jats:italic>, but the treatment of anti-Jagged1 neutralizing antibody attenuated it. Taken together, these results suggest that Jagged1 is a promoting molecule for macrophages against <jats:italic>H. pylori<\/jats:italic>, which will provide insight for exploring Jagged1 as a novel therapeutic target for the control of <jats:italic>H. pylori<\/jats:italic> infection.<\/jats:p>","DOI":"10.3389\/fmicb.2021.692832","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T09:36:04Z","timestamp":1625736964000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Notch Signaling Ligand Jagged1 Enhances Macrophage-Mediated Response to Helicobacter pylori"],"prefix":"10.3389","volume":"12","author":[{"given":"Junjie","family":"Wen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuxi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiqun","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaocong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiading","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyi","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sinan","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunshan","family":"Ning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1111\/j.1574-695x.2007.00338.x","article-title":"Host response to Helicobacter pylori infection before initiation of the adaptive immune response.","volume":"51","author":"Algood","year":"2007","journal-title":"FEMS Immunol. 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