{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T09:28:06Z","timestamp":1781602086481,"version":"3.54.5"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01A132406-03, R01A1065545-15"],"award-info":[{"award-number":["R01A132406-03, R01A1065545-15"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"RTI International (RTI Int'l) with USAID- STRIDE","award":["0213997-G-2015-003"],"award-info":[{"award-number":["0213997-G-2015-003"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,10,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Chlamydia trachomatis<\/jats:italic>\n              has adapted to subvert signaling in epithelial cells to ensure successful intracellular development. Interferon-\u03b3 (IFN\u03b3) produced by recruited lymphocytes signals through the JAK\/STAT pathway to restrict chlamydial growth in the genital tract. However, during\n              <jats:italic>Chlamydia<\/jats:italic>\n              infection\n              <jats:italic>in vitro<\/jats:italic>\n              , addition of IFN\u03b3 does not fully induce nuclear localization of its transcription factor STAT1 and expression of its target gene, IDO1. We hypothesize that this altered interferon response is a result of\n              <jats:italic>Chlamydia<\/jats:italic>\n              targeting components of the IFN\u03b3-JAK\/STAT pathway. To assess the ability of replicating\n              <jats:italic>Chlamydia<\/jats:italic>\n              to dampen interferon signaling, HEp2 human epithelial cells were infected with\n              <jats:italic>C. trachomatis<\/jats:italic>\n              serovar L2 for 24 hours prior to exposure to physiologically relevant levels of IFN\u03b3 (500 pg\/mL). This novel approach enabled us to observe reduced phospho-activation of both STAT1 and its kinase Janus Kinase 2 (JAK2) in infected cells compared with mock-infected cells. Importantly, basal JAK2 and STAT1 transcript and protein levels were dampened by infection even in the absence of interferon, which could have implications for cytokine signaling beyond IFN\u03b3. Additionally, target genes IRF1, GBP1, APOL3, IDO1, and SOCS1 were not fully induced in response to IFN\u03b3 exposure. Infection-dependent decreases in transcript, protein, and phosphoprotein were rescued when\n              <jats:italic>de novo<\/jats:italic>\n              bacterial protein synthesis was inhibited with chloramphenicol, restoring expression of IFN\u03b3-target genes. Similar\n              <jats:italic>Chlamydia<\/jats:italic>\n              -dependent dampening of STAT1 and JAK2 transcript levels was observed in infected HeLa and END1 endocervical cells and in HEp2s infected with\n              <jats:italic>C. trachomatis<\/jats:italic>\n              serovar D, suggesting a conserved mechanism of dampening the interferon response by reducing the availability of key signaling components.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              As an obligate intracellular pathogen that has evolved to infect the genital epithelium,\n              <jats:italic>Chlamydia<\/jats:italic>\n              has developed strategies to prevent detection and antimicrobial signaling in its host to ensure its survival and spread. A major player in clearing\n              <jats:italic>Chlamydia<\/jats:italic>\n              infections is the inflammatory cytokine interferon-\u03b3 (IFN\u03b3), which is produced by immune cells that are recruited to the site of infection. Reports of IFN\u03b3 levels in endocervical specimens from\n              <jats:italic>Chlamydia<\/jats:italic>\n              -infected patients range from 1 to 350 pg\/mL, while most\n              <jats:italic>in vitro<\/jats:italic>\n              studies of the effects of IFN\u03b3 on chlamydial growth have used 15\u201385-fold higher concentrations. By using physiologically relevant concentrations of IFN\u03b3, we were able to assess\n              <jats:italic>Chlamydia<\/jats:italic>\n              \u2019s ability to modulate its signaling. We found that\n              <jats:italic>Chlamydia<\/jats:italic>\n              decreases the expression of multiple components that are required for inducing gene expression by IFN\u03b3, providing a possible mechanism by which\n              <jats:italic>Chlamydia trachomatis<\/jats:italic>\n              can attenuate the immune response in the female genital tract to cause long-term infections.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.01834-24","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T13:02:12Z","timestamp":1724850132000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["<i>Chlamydia trachomatis<\/i>\n            modulates the expression of JAK-STAT signaling components to attenuate the type II interferon response of epithelial cells"],"prefix":"10.1128","volume":"15","author":[{"given":"Francis 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