{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T04:30:48Z","timestamp":1792989048115,"version":"4.5.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"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":[[2014,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IFN-\u03b2 has been implicated as an effector of oviduct pathology resulting from genital chlamydial infection in the mouse model. In this study, we investigated the role of cytosolic DNA and engagement of DNA sensors in IFN-\u03b2 expression during chlamydial infection. We determined that three-prime repair exonuclease-1, a host 3\u2032 to 5\u2032 exonuclease, reduced IFN-\u03b2 expression significantly during chlamydial infection using small interfering RNA and gene knockout fibroblasts, implicating cytosolic DNA as a ligand for this response. The DNA sensor cyclic GMP\u2013AMP synthase (cGAS) has been shown to bind cytosolic DNA to generate cyclic GMP\u2013AMP, which binds to the signaling adaptor stimulator of IFN genes (STING) to induce IFN-\u03b2 expression. We determined that cGAS is required for IFN-\u03b2 expression during chlamydial infection in multiple cell types. Interestingly, although infected cells deficient for STING or cGAS alone failed to induce IFN-\u03b2, coculture of cells depleted for either STING or cGAS rescued IFN-\u03b2 expression. These data demonstrate that cyclic GMP\u2013AMP produced in infected cGAS+STING\u2212 cells can migrate into adjacent cells via gap junctions to function in trans in cGAS\u2212STING+ cells. Furthermore, we observed cGAS localized in punctate regions on the cytosolic side of the chlamydial inclusion membrane in association with STING, indicating that chlamydial DNA is most likely recognized outside the inclusion as infection progresses. These novel findings provide evidence that cGAS-mediated DNA sensing directs IFN-\u03b2 expression during Chlamydia trachomatis infection and suggest that effectors from infected cells can directly upregulate IFN-\u03b2 expression in adjacent uninfected cells during in vivo infection, contributing to pathogenesis.<\/jats:p>","DOI":"10.4049\/jimmunol.1302718","type":"journal-article","created":{"date-parts":[[2014,7,29]],"date-time":"2014-07-29T02:50:00Z","timestamp":1406602200000},"page":"2394-2404","source":"Crossref","is-referenced-by-count":152,"title":["The DNA Sensor, Cyclic GMP\u2013AMP Synthase, Is Essential for Induction of IFN-\u03b2 during <i>Chlamydia trachomatis<\/i> Infection"],"prefix":"10.1093","volume":"193","author":[{"given":"Yugen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laxmi","family":"Yeruva","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Arkansas for Medical Sciences , Little Rock, AR 72202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Marinov","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Prantner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla B","family":"Wyrick","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Lupashin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Arkansas for Medical Sciences , Little Rock, AR 72205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma M","family":"Nagarajan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,9,1]]},"reference":[{"key":"2025030707320754700_r1","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1086\/367962","article-title":"Chlamydia trachomatis infection alters host cell transcription in diverse cellular pathways","volume":"187","author":"Xia","year":"2003","journal-title":"J. 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