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Recent studies have highlighted the importance of macrophage immunometabolism in their activation state and function. We have demonstrated that the cysteine-producing enzyme cystathionine \u03b3-lyase (CTH) is upregulated in humans and mice with\n                    <jats:italic>H. pylori<\/jats:italic>\n                    infection. Here, we show that induction of CTH in macrophages by\n                    <jats:italic>H. pylori<\/jats:italic>\n                    promoted persistent inflammation.\n                    <jats:italic>\n                      Cth\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice had reduced macrophage and T cell activation in\n                    <jats:italic>H. pylori<\/jats:italic>\n                    \u2013infected tissues, an altered metabolome, and decreased enrichment of immune-associated gene networks, culminating in decreased\n                    <jats:italic>H. pylori<\/jats:italic>\n                    \u2013induced gastritis. CTH is downstream of the proposed antiinflammatory molecule,\n                    <jats:italic>S<\/jats:italic>\n                    -adenosylmethionine (SAM). Whereas\n                    <jats:italic>\n                      Cth\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice exhibited gastric SAM accumulation, WT mice treated with SAM did not display protection against\n                    <jats:italic>H. pylori<\/jats:italic>\n                    \u2013induced inflammation. Instead, we demonstrated that\n                    <jats:italic>Cth<\/jats:italic>\n                    -deficient macrophages exhibited alterations in the proteome, decreased NF-\u03baB activation, diminished expression of macrophage activation markers, and impaired oxidative phosphorylation and glycolysis. Thus, through altering cellular respiration, CTH is a key enhancer of macrophage activation, contributing to a pathogenic inflammatory response that is the universal precursor for the development of\n                    <jats:italic>H. pylori<\/jats:italic>\n                    \u2013induced gastric disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.155338","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T12:25:40Z","timestamp":1652790340000},"source":"Crossref","is-referenced-by-count":29,"title":["Cystathionine \u03b3-lyase exacerbates Helicobacter pylori immunopathogenesis by promoting macrophage metabolic remodeling and activation"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9319-8268","authenticated-orcid":true,"given":"Yvonne L.","family":"Latour","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology,"},{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna C.","family":"Sierra","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and"},{"name":"Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan L.","family":"Finley","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Asim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3972-3914","authenticated-orcid":true,"given":"Daniel P.","family":"Barry","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2803-1365","authenticated-orcid":true,"given":"Margaret M.","family":"Allaman","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaddeus M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara M.","family":"McNamara","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and"},{"name":"Program in Cancer Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula B.","family":"Luis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4215-967X","authenticated-orcid":true,"given":"Claus","family":"Schneider","sequence":"additional","affiliation":[{"name":"Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee, USA."},{"name":"Department of Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1899-0319","authenticated-orcid":true,"given":"Justin","family":"Jacobse","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology,"},{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy A.","family":"Goettel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology,"},{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and"},{"name":"Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8002-4699","authenticated-orcid":true,"given":"M. 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