{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:47:53Z","timestamp":1791899273935,"version":"4.3.4"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01DK113043"],"award-info":[{"award-number":["K01DK113043"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01AI125181"],"award-info":[{"award-number":["P01AI125181"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30DK089502"],"award-info":[{"award-number":["P30DK089502"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD025244"],"award-info":[{"award-number":["S10OD025244"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Enterotoxigenic Escherichia coli<\/jats:italic>\n                      (ETEC) remains a leading cause of diarrheal disease in low- and middle-income countries, yet vaccine efforts have struggled to achieve broad and durable protection. To better understand early steps in host-pathogen interactions, we utilized human stem cell-derived jejunal organoid monolayers to compare epithelial responses to ETEC H10407 and E24377A, prototypical strains frequently used in controlled human infection challenges. Transcriptomic analysis revealed that H10407 uniquely stimulated a robust innate immune response, characterized by upregulation of TLR5-dependent genes, including\n                      <jats:italic toggle=\"yes\">IL-17C<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">CXCL6<\/jats:italic>\n                      . This response was found to be driven by sustained expression of flagella, the result of a naturally occurring\n                      <jats:italic toggle=\"yes\">fliZ<\/jats:italic>\n                      gene disruption in H10407, which allows flagellin production despite ample nutrient availability. Complementation with\n                      <jats:italic toggle=\"yes\">fliZ<\/jats:italic>\n                      restored repression of flagellar genes, confirming its regulatory role. In epithelial-macrophage co-cultures, H10407-expressed flagella enhanced macrophage sampling of bacteria as well as IL-6 production, effects that were not replicated by recombinant flagellin alone. However, exogenous flagellin did induce epithelial IL-17C release, a cytokine implicated in adaptive immune priming. These findings identify constitutive flagellar expression as a key factor in the heightened innate immune response and virulence of H10407, and highlight its potential utility in optimizing mucosal vaccine design against ETEC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00336-26","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:39:41Z","timestamp":1789655981000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Flagellar regulation in enterotoxigenic\n                    <i>E. coli<\/i>\n                    modulates innate immune activation"],"prefix":"10.1128","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3523-6318","authenticated-orcid":false,"given":"Pauline","family":"Ikpa","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Nengel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0715-2907","authenticated-orcid":true,"given":"James B.","family":"Kaper","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology & Immunology, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0477-8824","authenticated-orcid":true,"given":"Mark","family":"Donowitz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine","place":["Baltimore, 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