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Despite extensive efforts, there is no licensed\n                  <jats:italic>Shigella<\/jats:italic>\n                  vaccine, and due to the lack of tractable and physiological models, mechanisms of adaptive immunity to\n                  <jats:italic>Shigella<\/jats:italic>\n                  are poorly understood. Here, we establish a mouse model that permits mechanistic dissection of adaptive immunity to a physiological oral challenge with\n                  <jats:italic>Shigella<\/jats:italic>\n                  . We find primary\n                  <jats:italic>Shigella<\/jats:italic>\n                  infection confers robust cross-serotype protection against secondary challenge, in a manner strictly dependent on the adaptive immune compartment.\n                  <jats:italic>Shigella<\/jats:italic>\n                  infection induces\n                  <jats:italic>Shigella<\/jats:italic>\n                  -specific CD4\n                  <jats:sup>+<\/jats:sup>\n                  and CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells, but only CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells are required for protection. CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells produce IFN\n                  <jats:italic>\u03b3<\/jats:italic>\n                  upon secondary challenge, and help B cells produce\n                  <jats:italic>Shigella<\/jats:italic>\n                  -specific IgA. Neither anti-\n                  <jats:italic>Shigella<\/jats:italic>\n                  antibodies nor IFN\n                  <jats:italic>\u03b3<\/jats:italic>\n                  are individually required for immunity to\n                  <jats:italic>Shigella<\/jats:italic>\n                  , but loss of both eliminates protective immunity. Collectively, our results demonstrate that CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells orchestrate antibody and cytokine defense against shigellosis.\n                <\/jats:p>","DOI":"10.64898\/2026.09.08.750193","type":"posted-content","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:25:11Z","timestamp":1789431911000},"source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms of mucosal immunity to oral\n                  <i>Shigella<\/i>\n                  infection in a physiological mouse model"],"prefix":"10.64898","author":[{"given":"Janet Peace","family":"Babirye","sequence":"first","affiliation":[{"name":"Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma F.","family":"Lackner","sequence":"additional","affiliation":[{"name":"Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudyut","family":"Yuvaraj","sequence":"additional","affiliation":[{"name":"Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA"},{"name":"Howard Hughes Medical Institute, University of California, Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto A.","family":"Chavez","sequence":"additional","affiliation":[{"name":"Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA"},{"name":"Howard Hughes Medical Institute, University of California, Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte A.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Eislmayr","sequence":"additional","affiliation":[{"name":"Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan A.","family":"Fattinger","sequence":"additional","affiliation":[{"name":"Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7843-1503","authenticated-orcid":false,"given":"Dmitri I.","family":"Kotov","sequence":"additional","affiliation":[{"name":"Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, Andrew M. and Jane M. 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