{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T06:22:24Z","timestamp":1775197344416,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100007268","name":"Washington University in St. Louis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. National Institutes of Health","doi-asserted-by":"publisher","award":["HL105427"],"award-info":[{"award-number":["HL105427"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a leading cause of global morbidity and mortality. The only licensed TB vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG), has variable efficacy in protecting against pulmonary TB. Thus, the development of more effective TB vaccines is critical to control the TB epidemic. Specifically, vaccines delivered through the mucosal route are known to induce Th17 responses and provide superior protection against Mtb infection. However, already tested Th17-inducing mucosal adjuvants, such as heat-labile enterotoxins and cholera toxins, are not considered safe for use in humans. In the current study, we rationally screened adjuvants for their ability to induce Th17-polarizing cytokines in dendritic cells (DCs) and determined whether they could be used in a protective mucosal TB vaccine. Our new studies show that monophosphoryl lipid A (MPL), when used in combination with chitosan, potently induces Th17-polarizing cytokines in DCs and downstream Th17\/Th1 mucosal responses and confers significant protection in mice challenged with a clinical Mtb strain. Additionally, we show that both TLRs and the inflammasome pathways are activated in DCs by MPL-chitosan to mediate induction of Th17-polarizing cytokines. Together, our studies put forward the potential of a new, protective mucosal TB vaccine candidate, which incorporates safe adjuvants already approved for use in humans.<\/jats:p>","DOI":"10.1189\/jlb.4a0616-270r","type":"journal-article","created":{"date-parts":[[2017,3,4]],"date-time":"2017-03-04T01:40:28Z","timestamp":1488591628000},"page":"1373-1381","source":"Crossref","is-referenced-by-count":29,"title":["Rationalized design of a mucosal vaccine protects against <i>Mycobacterium tuberculosis<\/i> challenge in mice"],"prefix":"10.1093","volume":"101","author":[{"given":"Mushtaq","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology, Washington University in St. Louis , St. Louis, Missouri , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongmei","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University in St. Louis , St. Louis, Missouri , USA"},{"name":"School of Medicine, Yangzhou University , Yangzhou , People\u02c8s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Racquel","family":"Domingo-Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University in St. Louis , St. Louis, Missouri , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shibali","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University in St. Louis , St. Louis, Missouri , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin L","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University in St. Louis , St. Louis, Missouri , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Rangel-Moreno","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center , Rochester, New York , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uma M","family":"Nagarajan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Microbiology\/Immunology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shabaana A","family":"Khader","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University in St. Louis , St. Louis, Missouri , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,3,3]]},"reference":[{"key":"2023011712222536800_B1","volume-title":"Global Tuberculosis Report 2015","author":"World Health Organization"},{"key":"2023011712222536800_B2","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1146\/annurev-publhealth-031912-114431","article-title":"Prospects for tuberculosis elimination","volume":"34","author":"Dye","year":"2013","journal-title":"Annu. 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Immunol."},{"key":"2023011712222536800_B7","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/ni1449","article-title":"IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge","volume":"8","author":"Khader","year":"2007","journal-title":"Nat. Immunol."},{"key":"2023011712222536800_B8","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.coi.2014.02.003","article-title":"Novel vaccine approaches for protection against intracellular pathogens","volume":"28","author":"Griffiths","year":"2014","journal-title":"Curr. Opin. 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