{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:54:07Z","timestamp":1790952847207,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010333","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000}}],"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["AI103422"],"award-info":[{"award-number":["AI103422"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32 AI060555."],"award-info":[{"award-number":["T32 AI060555."]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Protective immune responses to<jats:italic>Chlamydia<\/jats:italic>infection within the female reproductive tract (FRT) are incompletely understood. MHC class II-restricted CD4 Th1 responses are believed to be vital for bacterial clearance due to their capacity to secrete IFN-\u03b3, but an essential requirement for T-bet-expressing Th1 cells has yet to be demonstrated in the mouse model of<jats:italic>Chlamydia<\/jats:italic>infection. Here, we investigated the role of T-bet and IFN-\u03b3 in primary clearance of<jats:italic>Chlamydia<\/jats:italic>after FRT infection. Surprisingly, IFN-\u03b3 producing CD4 T cells from the FRT expressed low levels of T-bet throughout infection, suggesting that classical T-bet-expressing Th1 cells are inefficiently generated and therefore unlikely to participate in bacteria clearance. Furthermore, mice deficient in T-bet expression or with a CD4-specific T-bet deficiency cleared FRT infection similarly to wild-type controls. T-bet-deficient mice displayed significant skewing of FRT CD4 T cells towards Th17 responses, demonstrating that compensatory effector pathways are generated in the absence of Th1 cells. In marked contrast, IFN-\u03b3-, and IFN-\u03b3R-deficient mice were able to reduce FRT bacterial burdens, but suffered systemic bacterial dissemination and 100% mortality. Together, these data demonstrate that IFN-\u03b3 signaling is essential to protect mice from fatal systemic disease, but that classical T-bet-expressing Th1 cells are non-essential for primary clearance within the FRT. Exploring the protective contribution of Th1 cells versus other CD4 effector lineages could provide important information for the generation of new<jats:italic>Chlamydia<\/jats:italic>vaccines.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010333","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T18:41:02Z","timestamp":1645641662000},"page":"e1010333","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Th1 cells are dispensable for primary clearance of Chlamydia from the female reproductive tract of mice"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8313-0702","authenticated-orcid":true,"given":"Jordan A.","family":"Rixon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire 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