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In response to\n              <jats:italic>C. rodentium<\/jats:italic>\n              infection, innate lymphoid cells and T cells secrete interleukin (IL)-22, a cytokine that promotes mucosal barrier function. IL-22 plays a pivotal role in enabling mice to survive and recover from\n              <jats:italic>C. rodentium<\/jats:italic>\n              infection, although the exact mechanisms involved remain incompletely understood. Here, we investigated whether particular components of the host response downstream of IL-22 contribute to the cytokine\u2019s protective effects during\n              <jats:italic>C. rodentium<\/jats:italic>\n              infection. In line with previous research, mice lacking the IL-22 gene (\n              <jats:italic>Il22<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice) were highly susceptible to\n              <jats:italic>C. rodentium<\/jats:italic>\n              infection. To elucidate the role of specific antimicrobial proteins modulated by IL-22, we infected the following knockout mice:\n              <jats:italic>S100A9<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (calprotectin),\n              <jats:italic>Lcn2<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (lipocalin-2),\n              <jats:italic>Reg3b<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (Reg3\u03b2),\n              <jats:italic>Reg3g<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (Reg3\u03b3), and\n              <jats:italic>C3<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (C3). All knockout mice tested displayed a considerable level of resistance to\n              <jats:italic>C. rodentium<\/jats:italic>\n              infection, and none phenocopied the lethality observed in\n              <jats:italic>Il22<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. By investigating another arm of the IL-22 response, we observed that\n              <jats:italic>C. rodentium<\/jats:italic>\n              -infected\n              <jats:italic>\n                Il22\n                <jats:sup>\u2212\/<\/jats:sup>\n              <\/jats:italic>\n              <jats:sup>\u2212<\/jats:sup>\n              mice exhibited an overall decrease in gene expression related to intestinal barrier integrity as well as significantly elevated colonic inflammation, gut permeability, and pathogen levels in the spleen. Taken together, these results indicate that host resistance to lethal\n              <jats:italic>C. rodentium<\/jats:italic>\n              infection may depend on multiple antimicrobial responses acting in concert, or that other IL-22-regulated processes, such as tissue repair and maintenance of epithelial integrity, play crucial roles in host defense to attaching and effacing pathogens.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/iai.00099-24","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T13:01:42Z","timestamp":1711976502000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["IL-22-dependent responses and their role during\n            <i>Citrobacter rodentium<\/i>\n            infection"],"prefix":"10.1128","volume":"92","author":[{"given":"Karine","family":"Melchior","sequence":"first","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California, USA"},{"name":"School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2377-6509","authenticated-orcid":false,"given":"Romana R.","family":"Gerner","sequence":"additional","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California, USA"},{"name":"School of Life Sciences, ZIEL \u2013 Institute for Food and Health, Freising-Weihenstephan, Technical University of Munich, Munich, Germany"},{"name":"Department of Internal Medicine III, University Hospital rechts der Isar, Technical University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzana","family":"Hossain","sequence":"additional","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9683-9278","authenticated-orcid":false,"given":"Sean-Paul","family":"Nuccio","sequence":"additional","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0689-4119","authenticated-orcid":false,"given":"Cristiano Gallina","family":"Moreira","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara, S\u00e3o Paulo, Brazil"},{"name":"Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6487-4215","authenticated-orcid":false,"given":"Manuela","family":"Raffatellu","sequence":"additional","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California, USA"},{"name":"Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA"},{"name":"Chiba University-UC San Diego Center for Mucosal Immunology, Allergy, and Vaccines (CU-UCSD cMAV), La Jolla, California, 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