{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:37:48Z","timestamp":1790653068581,"version":"4.1.0"},"posted":{"date-parts":[[2023,7,7]]},"group-title":"Microbiology","reference-count":76,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The intracellular Gram-negative bacterium\n                  <jats:italic>Coxiella burnetii<\/jats:italic>\n                  replicates within macrophages and causes a zoonotic disease known as Q fever. In murine macrophages, the cytokine tumor necrosis factor (TNF) is critical for restriction of intracellular\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  replication. Here, we show that TNF collaborates with type I interferon (IFN) signaling for maximal control of\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  . We found that TNF and type I IFN upregulate the expression of the metabolic enzyme immune responsive gene 1 (IRG1), also known as cis-aconitate decarboxylase 1 (ACOD1), and that IRG1 is required to restrict\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  T4SS translocation and replication within macrophages. Further, we show that itaconic acid, the metabolic product of IRG1, restricts\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  replication both intracellularly and in axenic culture. These data reveal that TNF and type I IFN upregulate the IRG1-itaconate pathway to restrict intracellular\n                  <jats:italic>C<\/jats:italic>\n                  .\n                  <jats:italic>burnetii<\/jats:italic>\n                  replication within murine macrophages.\n                <\/jats:p>","DOI":"10.1101\/2023.07.07.548079","type":"posted-content","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T15:40:21Z","timestamp":1688744421000},"source":"Crossref","is-referenced-by-count":4,"title":["TNF and type I IFN induction of the IRG1-itaconate pathway restricts\n                  <i>Coxiella burnetii<\/i>\n                  replication within mouse macrophages"],"prefix":"10.64898","author":[{"given":"Mark A.","family":"Boyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Lopes 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