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Here we show that type I IFN suppresses the antibacterial activity of phagocytes to promote systemic <jats:italic>Lm<\/jats:italic> infection. Mechanistically, type I IFN suppresses phagosome maturation and proteolysis of <jats:italic>Lm<\/jats:italic> virulence factors ActA and LLO, thereby promoting phagosome escape and cell-to-cell spread; the antiviral protein, IFN-induced transmembrane protein 3 (IFITM3), is required for this type I IFN-mediated alteration. <jats:italic>Ifitm3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice are resistant to systemic infection by <jats:italic>Lm<\/jats:italic>, displaying decreased bacterial spread in tissues, and increased immune cell recruitment and pro-inflammatory cytokine signaling. Together, our findings show how an antiviral mechanism in phagocytes can be exploited by bacterial pathogens, and implicate IFITM3 as a potential antimicrobial therapeutic target.<\/jats:p>","DOI":"10.1038\/s41467-021-24982-0","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T10:05:02Z","timestamp":1629194702000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Listeria exploits IFITM3 to suppress antibacterial activity in phagocytes"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6051-3786","authenticated-orcid":false,"given":"Joel M. 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