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Mechanisms responsible for the divergent clinical manifestations of nontyphoidal and enteric fever\n              <jats:italic>Salmonella<\/jats:italic>\n              infections have remained elusive. Here, we show that\n              <jats:italic>S<\/jats:italic>\n              . Typhi and\n              <jats:italic>S<\/jats:italic>\n              . Paratyphi A can persist within human macrophages, whereas\n              <jats:italic>S<\/jats:italic>\n              . Typhimurium rapidly induces apoptotic macrophage cell death that is dependent on\n              <jats:italic>Salmonella<\/jats:italic>\n              pathogenicity island 2 (SPI2).\n              <jats:italic>S<\/jats:italic>\n              . Typhi and\n              <jats:italic>S<\/jats:italic>\n              . Paratyphi A lack 12 specific SPI2 effectors with pro-apoptotic functions, including nine that target nuclear factor \u03baB (NF-\u03baB). Pharmacologic inhibition of NF-\u03baB or heterologous expression of the SPI2 effectors GogA or GtgA restores apoptosis of\n              <jats:italic>S<\/jats:italic>\n              . Typhi-infected macrophages. In addition, the absence of the SPI2 effector SarA results in deficient signal transducer and activator of transcription 1 (STAT1) activation and interleukin 12 production, leading to impaired T\n              <jats:sub>H<\/jats:sub>\n              1 responses in macrophages and humanized mice. The absence of specific nontyphoidal SPI2 effectors may allow\n              <jats:italic>S<\/jats:italic>\n              . Typhi and\n              <jats:italic>S<\/jats:italic>\n              . Paratyphi A to cause chronic infections.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Salmonella enterica is a common cause of gastrointestinal infections worldwide. The serovars\n              <jats:italic>Salmonella<\/jats:italic>\n              Typhi and\n              <jats:italic>Salmonella<\/jats:italic>\n              Paratyphi A cause a distinctive systemic illness called enteric fever, whose pathogenesis is incompletely understood. Here, we show that enteric fever\n              <jats:italic>Salmonella<\/jats:italic>\n              serovars lack 12 specific virulence factors possessed by nontyphoidal\n              <jats:italic>Salmonella<\/jats:italic>\n              serovars, which allow the enteric fever serovars to persist within human macrophages. We propose that this fundamental difference in the interaction of\n              <jats:italic>Salmonella<\/jats:italic>\n              with human macrophages is responsible for the chronicity of typhoid and paratyphoid fever, suggesting that targeting the nuclear factor \u03baB (NF-\u03baB) complex responsible for macrophage survival could facilitate the clearance of persistent bacterial infections.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.00454-24","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T13:01:46Z","timestamp":1712754106000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Nuclear factor kappa B-dependent persistence of\n            <i>Salmonella<\/i>\n            Typhi and Paratyphi in human macrophages"],"prefix":"10.1128","volume":"15","author":[{"given":"Taylor A.","family":"Stepien","sequence":"first","affiliation":[{"name":"Department of Global Health, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa A.","family":"Singletary","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fermin E.","family":"Guerra","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce E.","family":"Karlinsey","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Libby","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L.","family":"Jaslow","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret R.","family":"Gaggioli","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle D.","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0113-5981","authenticated-orcid":true,"given":"Dennis 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