{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T04:26:09Z","timestamp":1771475169435,"version":"3.50.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T00:00:00Z","timestamp":1598227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK099071"],"award-info":[{"award-number":["DK099071"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK083890"],"award-info":[{"award-number":["DK083890"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["1-19-JDF-077"],"award-info":[{"award-number":["1-19-JDF-077"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Bacterial flagellin is a major target of innate and adaptive immunity, both of which can promote and\/or compensate for deficiencies in each other\u2019s function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To investigate the role of innate immune detection of flagellin irrespective of adaptive immunity, we examined the consequences of loss of Toll-like receptor 5 (T5) and\/or Nod-like receptor 4 (N4) upon a Rag1-deficient background.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Mice lacking Toll-like receptor 5 and Rag1 (T5\/Rag-DKO) exhibited frequent lethal Pasteurellaceae-containing abscesses that prevented breeding of these mice. Mice lacking Toll-like receptor 5, Nod-like receptor 4, and Rag1 (T5\/N4\/Rag-TKO) also resulted in sporadic lethal abdominal abscesses caused by similar Pasteurellaceae. In the absence of such infections, relative to Rag1-KO, T5\/N4\/Rag-TKO mice exhibited microbiota encroachment, low-grade inflammation, microbiota dysbiosis, and, moreover were highly prone to Citrobacter infection and developed severe colitis when adoptively transferred with colitogenic T cells. Relative proneness of T5\/N4\/Rag-TKO mice to T-cell colitis was ablated by antibiotics while fecal microbiota transplant from T5\/N4\/Rag-TKO mice to wild-type mice transferred proneness to Citrobacter infection, indicating that dysbiosis in T5\/N4\/Rag-TKO mice contributed to these phenotypes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results demonstrate a critical role for innate immune detection of flagellin, especially in the intestinal tract and particularly in hosts deficient in adaptive immunity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaa521","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T19:12:54Z","timestamp":1597432374000},"page":"1478-1487","source":"Crossref","is-referenced-by-count":13,"title":["Critical Role of Innate Immunity to Flagellin in the Absence of Adaptive Immunity"],"prefix":"10.1093","volume":"223","author":[{"given":"Jun","family":"Zou","sequence":"first","affiliation":[{"name":"Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenda","family":"Shi","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matam","family":"Vijay-Kumar","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benoit","family":"Chassaing","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA"},{"name":"Neuroscience Institute, Georgia State University, Atlanta, Georgia, USA"},{"name":"French National Institute of Health and Medical Research - INSERM, U1016, team \u201cMucosal microbiota in chronic inflammatory diseases,\u201d Paris, France"},{"name":"Universit\u00e9 de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew T","family":"Gewirtz","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,8,24]]},"reference":[{"key":"2021042315534963000_CIT0001","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1097\/01.mog.0000194791.59337.28","article-title":"Flag in the crossroads: flagellin modulates innate and adaptive immunity","volume":"22","author":"Gewirtz","year":"2006","journal-title":"Curr Opin Gastroenterol"},{"key":"2021042315534963000_CIT0002","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/mi.2009.9","article-title":"Flagellin: key target of mucosal innate immunity","volume":"2","author":"Vijay-Kumar","year":"2009","journal-title":"Mucosal Immunol"},{"key":"2021042315534963000_CIT0003","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00281-007-0078-z","article-title":"TLR5 and Ipaf: dual sensors of bacterial flagellin in the innate immune system","volume":"29","author":"Miao","year":"2007","journal-title":"Semin Immunopathol"},{"key":"2021042315534963000_CIT0004","doi-asserted-by":"crossref","first-page":"986","DOI":"10.4049\/jimmunol.164.2.986","article-title":"Characterization of CD4+ T cell responses during natural infection with Salmonella typhimurium","volume":"164","author":"McSorley","year":"2000","journal-title":"J Immunol"},{"key":"2021042315534963000_CIT0005","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1172\/JCI200420295","article-title":"Bacterial flagellin is a dominant antigen in Crohn disease","volume":"113","author":"Lodes","year":"2004","journal-title":"J Clin Invest"},{"key":"2021042315534963000_CIT0006","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.chom.2013.10.009","article-title":"Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut","volume":"14","author":"Cullender","year":"2013","journal-title":"Cell Host Microbe"},{"key":"2021042315534963000_CIT0007","doi-asserted-by":"crossref","first-page":"5650","DOI":"10.1038\/s41467-019-13538-y","article-title":"Flagellin-elicited adaptive immunity suppresses flagellated microbiota and vaccinates against chronic inflammatory diseases","volume":"10","author":"Tran","year":"2019","journal-title":"Nat Commun"},{"key":"2021042315534963000_CIT0008","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.4049\/jimmunol.167.4.1882","article-title":"Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression","volume":"167","author":"Gewirtz","year":"2001","journal-title":"J Immunol"},{"key":"2021042315534963000_CIT0009","doi-asserted-by":"crossref","first-page":"7184","DOI":"10.4049\/jimmunol.180.11.7184","article-title":"Both radioresistant and hemopoietic cells promote innate and adaptive immune responses to flagellin","volume":"180","author":"Sanders","year":"2008","journal-title":"J Immunol"},{"key":"2021042315534963000_CIT0010","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/ni1362","article-title":"Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells","volume":"7","author":"Uematsu","year":"2006","journal-title":"Nat Immunol"},{"key":"2021042315534963000_CIT0011","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/ni.2263","article-title":"NLRC4-driven production of IL-1\u03b2 discriminates between pathogenic and commensal bacteria and promotes host intestinal defense","volume":"13","author":"Franchi","year":"2012","journal-title":"Nat Immunol"},{"key":"2021042315534963000_CIT0012","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1126\/science.1256999","article-title":"Viral infection. 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