{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:08:16Z","timestamp":1780430896898,"version":"3.54.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":1954,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bacterial flagellin is a well-known agonist of the innate immune system that induces proinflammatory responses through the TLR5 and Naip5\/6 recognition pathways. Several clinical trials investigating flagellin fusion proteins have demonstrated promising results for inducing protective immunity toward influenza virus, which has been largely attributed to flagellin\u2019s ability to activate TLR5. Our laboratory previously demonstrated that the Salmonella enterica serovar Typhimurium flagellin protein, FliC, induces Ab responses in mice through a third pathway that is independent of TLR5, Casp1\/11, and MyD88. In this study, we further define the structural features of FliC that contribute to this unknown third pathway. By destroying the Naip5\/6 and TLR5 recognition sites, we demonstrate that neither were required for the TLR5-, inflammasome- and MyD88-independent Ab responses toward FliC. In contrast, deletion of FliC\u2019s D3 or D0\/D1 domains eliminated primary anti-flagellin Ab responses. For optimal primary and secondary anti-flagellin Ab responses we show that TLR5, inflammasome recognition, and the D3 domain of FliC are essential for flagellin\u2019s robust immunogenicity. Our data demonstrate that the D3 domain of FliC influences immunogenicity independent of the known innate recognition sites in the D0\/D1 domains to augment Ab production. Our results suggest full-length FliC is critical for optimal immunogenicity and Ab responses in flagellin-based vaccines.<\/jats:p>","DOI":"10.4049\/immunohorizons.1800061","type":"journal-article","created":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T19:39:16Z","timestamp":1567712356000},"page":"422-432","source":"Crossref","is-referenced-by-count":19,"title":["FliC\u2019s Hypervariable D3 Domain Is Required for Robust Anti-Flagellin Primary Antibody Responses"],"prefix":"10.1093","volume":"3","author":[{"given":"Am\u00e9rico H","family":"L\u00f3pez-Yglesias","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Washington , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6202-1382","authenticated-orcid":false,"given":"Chun-Chi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Washington , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Washington , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Washington , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"VandenBos","sequence":"additional","affiliation":[{"name":"Division of Basic Sciences, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1338-2189","authenticated-orcid":false,"given":"Roland K","family":"Strong","sequence":"additional","affiliation":[{"name":"Division of Basic Sciences, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly D","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Washington , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,9,6]]},"reference":[{"key":"2025010608415728700_r1","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"2025010608415728700_r2","doi-asserted-by":"crossref","first-page":"9577","DOI":"10.1073\/pnas.0502272102","article-title":"The evolution of vertebrate toll-like receptors","volume":"102","author":"Roach","year":"2005","journal-title":"Proc. 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