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Here, we identify the enzyme cis\u2010aconitate decarboxylase 1 (ACOD1 or IRG1) and its product itaconate as protective host immune pathway in Q fever. Infection of mice with\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    induced expression of several anti\u2010microbial candidate genes, including\n                    <jats:italic>Acod1<\/jats:italic>\n                    . In macrophages,\n                    <jats:italic>Acod1<\/jats:italic>\n                    was essential for restricting\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    replication, while other antimicrobial pathways were dispensable. Intratracheal or intraperitoneal infection of\n                    <jats:italic>Acod1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice caused increased\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    burden, weight loss and stronger inflammatory gene expression. Exogenously added itaconate restored pathogen control in\n                    <jats:italic>Acod1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mouse macrophages and blocked replication in human macrophages. In axenic cultures, itaconate directly inhibited growth of\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    . Finally, treatment of infected\n                    <jats:italic>Acod1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice with itaconate efficiently reduced the tissue pathogen load. Thus, ACOD1\u2010derived itaconate is a key factor in the macrophage\u2010mediated defense against\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    and may be exploited for novel therapeutic approaches in chronic Q fever.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202215931","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T10:12:11Z","timestamp":1670407931000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Macrophages inhibit Coxiella burnetii by the ACOD1\u2010itaconate pathway for containment of Q fever"],"prefix":"10.1038","volume":"15","author":[{"given":"Lisa","family":"Kohl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9732-3986","authenticated-orcid":false,"given":"Md Nur A 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