{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:56:48Z","timestamp":1791071808630,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection in the United States and a significant health burden worldwide. Protection from Chlamydia infection in the genital mucosa is dependent on IFN-\u03b3 derived from CD4+ Th1 cells. These CD4+ T cells must home successfully to the genital tract to exert their effector function and decrease C. trachomatis burden. Although adhesion receptors expressed by CD4+ T cells in the genital tract have been characterized, the integrin receptor required for Chlamydia-specific CD4+ T cell\u2013mediated protection has not been explored. In this study, we demonstrate that C. trachomatis infection of the upper genital tract results in recruitment of Chlamydia-specific CD4+ T cells robustly expressing the integrin \u03b14\u03b21. Interfering with \u03b14\u03b21, but not \u03b14\u03b27, function resulted in defective CD4+ T cell trafficking to the uterus and high bacterial load. We conclude that integrin \u03b14\u03b21 is necessary for CD4+ T cell\u2013mediated protection against C. trachomatis infection in the genital mucosa. By identifying homing molecules required for successful CD4+ T cell trafficking to C. trachomatis\u2013infected tissues, we will be better equipped to design vaccines that elicit sterilizing, long-lasting immunity without inducing immune pathologies in the upper genital tract.<\/jats:p>","DOI":"10.4049\/jimmunol.1303238","type":"journal-article","created":{"date-parts":[[2014,3,22]],"date-time":"2014-03-22T00:48:25Z","timestamp":1395449305000},"page":"4284-4293","source":"Crossref","is-referenced-by-count":34,"title":["Integrin \u03b14\u03b21 Is Necessary for CD4+ T Cell\u2013Mediated Protection against Genital <i>Chlamydia trachomatis<\/i> Infection"],"prefix":"10.1093","volume":"192","author":[{"given":"Sergio J","family":"Davila","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunobiology, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J","family":"Olive","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunobiology, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael N","family":"Starnbach","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunobiology, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,5,1]]},"reference":[{"key":"2025032404272868700_r1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/nri1551","article-title":"Immunology of Chlamydia infection: implications for a Chlamydia trachomatis vaccine","volume":"5","author":"Brunham","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"2025032404272868700_r2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1136\/sti.75.1.21","article-title":"Pathogenesis of Chlamydia induced pelvic inflammatory disease","volume":"75","author":"Cohen","year":"1999","journal-title":"Sex. Transm. Infect."},{"key":"2025032404272868700_r3","first-page":"9","article-title":"Immune-mediated control of Chlamydia infection","volume":"10","author":"Roan","year":"2008","journal-title":"Cell. Microbiol."},{"key":"2025032404272868700_r4","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.4049\/jimmunol.162.6.3541","article-title":"Differential sensitivity of distinct Chlamydia trachomatis isolates to IFN-\u03b3-mediated inhibition","volume":"162","author":"Perry","year":"1999","journal-title":"J. Immunol."},{"key":"2025032404272868700_r5","doi-asserted-by":"crossref","first-page":"5529","DOI":"10.4049\/jimmunol.150.12.5529","article-title":"IFN-\u03b3-mediated antimicrobial response. Indoleamine 2,3-dioxygenase-deficient mutant host cells no longer inhibit intracellular Chlamydia spp. or Toxoplasma growth","volume":"150","author":"Thomas","year":"1993","journal-title":"J. Immunol."},{"key":"2025032404272868700_r6","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1128\/iai.61.2.491-497.1993","article-title":"Gamma interferon-induced nitric oxide production reduces Chlamydia trachomatis infectivity in McCoy cells","volume":"61","author":"Mayer","year":"1993","journal-title":"Infect. Immun."},{"key":"2025032404272868700_r7","doi-asserted-by":"crossref","first-page":"10658","DOI":"10.1073\/pnas.0504198102","article-title":"Chlamydial IFN-\u03b3 immune evasion is linked to host infection tropism","volume":"102","author":"Nelson","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404272868700_r8","doi-asserted-by":"crossref","first-page":"6237","DOI":"10.4049\/jimmunol.180.9.6237","article-title":"Chlamydia muridarum evades growth restriction by the IFN-\u03b3-inducible host resistance factor Irgb10","volume":"180","author":"Coers","year":"2008","journal-title":"J. Immunol."},{"key":"2025032404272868700_r9","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.4049\/jimmunol.0900295","article-title":"T cell responses in the absence of IFN-\u03b3 exacerbate uterine infection with Chlamydia trachomatis","volume":"183","author":"Gondek","year":"2009","journal-title":"J. Immunol."},{"key":"2025032404272868700_r10","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.4049\/jimmunol.1103032","article-title":"CD4+ T cells are necessary and sufficient to confer protection against Chlamydia trachomatis infection in the murine upper genital tract","volume":"189","author":"Gondek","year":"2012","journal-title":"J. Immunol."},{"key":"2025032404272868700_r11","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1046\/j.1365-2567.2001.01167.x","article-title":"Immunological memory in B-cell-deficient mice conveys long-lasting protection against genital tract infection with Chlamydia trachomatis by rapid recruitment of T cells","volume":"102","author":"Johansson","year":"2001","journal-title":"Immunology"},{"key":"2025032404272868700_r12","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0092-8674(94)90337-9","article-title":"Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm","volume":"76","author":"Springer","year":"1994","journal-title":"Cell"},{"key":"2025032404272868700_r13","first-page":"683","article-title":"Integrins: bidirectional, allosteric signaling machines","volume":"110","author":"Richard","year":"2002","journal-title":"Cell"},{"key":"2025032404272868700_r14","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/331086a0","article-title":"ICAM-1 a ligand for LFA-1-dependent adhesion of B, T and myeloid cells","volume":"331","author":"Makgoba","year":"1988","journal-title":"Nature"},{"key":"2025032404272868700_r15","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev.iy.05.040187.001255","article-title":"The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system","volume":"5","author":"Springer","year":"1987","journal-title":"Annu. Rev. Immunol."},{"key":"2025032404272868700_r16","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nature01726","article-title":"Selective imprinting of gut-homing T cells by Peyer\u2019s patch dendritic cells","volume":"424","author":"Mora","year":"2003","journal-title":"Nature"},{"key":"2025032404272868700_r17","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/356063a0","article-title":"Prevention of experimental autoimmune encephalomyelitis by antibodies against \u03b14\u03b21 integrin","volume":"356","author":"Yednock","year":"1992","journal-title":"Nature"},{"key":"2025032404272868700_r18","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1073\/pnas.0808909106","article-title":"Beta1 integrins differentially control extravasation of inflammatory cell subsets into the CNS during autoimmunity","volume":"106","author":"Bauer","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404272868700_r19","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1056\/NEJMoa042982","article-title":"Treatment of ulcerative colitis with a humanized antibody to the \u03b14\u03b27 integrin","volume":"352","author":"Feagan","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"2025032404272868700_r20","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/nrd1752","article-title":"Blocking adhesion molecules as therapy for multiple sclerosis: natalizumab","volume":"4","author":"Steinman","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"2025032404272868700_r21","doi-asserted-by":"crossref","first-page":"12069","DOI":"10.1073\/pnas.0603866103","article-title":"Monitoring the T cell response to genital tract infection","volume":"103","author":"Roan","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404272868700_r22","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/mi.2010.58","article-title":"CXCR3 and CCR5 are both required for T cell-mediated protection against C. trachomatis infection in the murine genital mucosa","volume":"4","author":"Olive","year":"2011","journal-title":"Mucosal Immunol."},{"key":"2025032404272868700_r23","doi-asserted-by":"crossref","first-page":"5587","DOI":"10.1128\/IAI.68.10.5587-5594.2000","article-title":"Expression of mucosal homing receptor \u03b14\u03b27 is associated with enhanced migration to the Chlamydia-infected murine genital mucosa in vivo","volume":"68","author":"Hawkins","year":"2000","journal-title":"Infect. Immun."},{"key":"2025032404272868700_r24","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1111\/j.1600-0897.2009.00704.x","article-title":"Two different homing pathways involving integrin \u03b27 and E-selectin significantly influence trafficking of CD4 cells to the genital tract following Chlamydia muridarum infection","volume":"61","author":"Kelly","year":"2009","journal-title":"Am. J. Reprod. Immunol."},{"key":"2025032404272868700_r25","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.4049\/jimmunol.160.6.2905","article-title":"Distinct homing pathways direct T lymphocytes to the genital and intestinal mucosae in Chlamydia-infected mice","volume":"160","author":"Perry","year":"1998","journal-title":"J. Immunol."},{"key":"2025032404272868700_r26","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1002\/eji.200940017","article-title":"Bystander stimulation of activated CD4+ T cells of unrelated specificity following a booster vaccination with tetanus toxoid","volume":"40","author":"Di Genova","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"2025032404272868700_r27","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1056\/NEJM200010053431407","article-title":"T-cell function and migration. Two sides of the same coin","volume":"343","author":"von Andrian","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"2025032404272868700_r28","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1101\/gad.9.15.1896","article-title":"Consequences of lack of \u03b21 integrin gene expression in mice","volume":"9","author":"F\u00e4ssler","year":"1995","journal-title":"Genes Dev."},{"key":"2025032404272868700_r29","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.4049\/jimmunol.0902407","article-title":"Control of \u03b14\u03b27 integrin expression and CD4 T cell homing by the \u03b21 integrin subunit","volume":"184","author":"DeNucci","year":"2010","journal-title":"J. Immunol."},{"key":"2025032404272868700_r30","doi-asserted-by":"crossref","first-page":"5198","DOI":"10.1128\/iai.65.12.5198-5208.1997","article-title":"Identification of homing receptors that mediate the recruitment of CD4 T cells to the genital tract following intravaginal infection with Chlamydia trachomatis","volume":"65","author":"Kelly","year":"1997","journal-title":"Infect. Immun."},{"key":"2025032404272868700_r31","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.4049\/jimmunol.152.6.2675","article-title":"Naive versus memory CD4 T cell response to antigen. Memory cells are less dependent on accessory cell costimulation and can respond to many antigen-presenting cell types including resting B cells","volume":"152","author":"Croft","year":"1994","journal-title":"J. Immunol."},{"key":"2025032404272868700_r32","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.immuni.2004.08.011","article-title":"Retinoic acid imprints gut-homing specificity on T cells","volume":"21","author":"Iwata","year":"2004","journal-title":"Immunity"},{"key":"2025032404272868700_r33","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1084\/jem.20122762","article-title":"Lung dendritic cells induce migration of protective T cells to the gastrointestinal tract","volume":"210","author":"Ruane","year":"2013","journal-title":"J. Exp. Med."},{"key":"2025032404272868700_r34","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/0092-8674(90)90661-W","article-title":"VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4\/fibronectin binding site","volume":"60","author":"Mariano","year":"1990","journal-title":"Cell"},{"key":"2025032404272868700_r35","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1083\/jcb.128.6.1243","article-title":"The integrin VLA-4 supports tethering and rolling in flow on VCAM-1","volume":"128","author":"Alon","year":"1995","journal-title":"J. Cell Biol."},{"key":"2025032404272868700_r36","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1056\/NEJMe020157","article-title":"\u03b14 Integrins as therapeutic targets in autoimmune disease","volume":"348","author":"von Andrian","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"2025032404272868700_r37","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1046\/j.1365-2567.1999.00675.x","article-title":"Distribution of lymphocytes and adhesion molecules in human cervix and vagina","volume":"96","author":"Johansson","year":"1999","journal-title":"Immunology"},{"key":"2025032404272868700_r38","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1046\/j.1365-2567.2000.00980.x","article-title":"Interferon-\u03b3 up-regulates intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and recruits lymphocytes into the vagina of immune mice challenged with herpes simplex virus-2","volume":"99","author":"Parr","year":"2000","journal-title":"Immunology"},{"key":"2025032404272868700_r39","doi-asserted-by":"crossref","first-page":"6911","DOI":"10.4049\/jimmunol.1002596","article-title":"Chlamydia-specific CD4 T cell clones control Chlamydia muridarum replication in epithelial cells by nitric oxide-dependent and -independent mechanisms","volume":"185","author":"Jayarapu","year":"2010","journal-title":"J. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/192\/9\/4284\/62510276\/1303238.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/192\/9\/4284\/62510276\/1303238.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T09:56:03Z","timestamp":1742810163000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/192\/9\/4284\/8001546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,1]]},"references-count":39,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2014,5,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1303238","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,5]]},"published":{"date-parts":[[2014,5,1]]}}}