{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:35:54Z","timestamp":1793900154742,"version":"4.8.0"},"reference-count":73,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["20-PAMR-0011 TheraEPI"],"award-info":[{"award-number":["20-PAMR-0011 TheraEPI"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006364","name":"Institut National Du Cancer","doi-asserted-by":"publisher","award":["INCA_16719"],"award-info":[{"award-number":["INCA_16719"]}],"id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n The inflammation induced by\n Chlamydia trachomatis<\/jats:italic>\n infection in the female genital tract can have severe consequences. Recent observations in women and mice infected with\n Chlamydia<\/jats:italic>\n suggest that type I interferon (IFN-I) may have deleterious effects. This study aimed to elucidate the consequences of IFN-I production on\n C. trachomatis<\/jats:italic>\n -induced inflammation in epithelial cells and the molecular pathway(s) involved. We showed that the combination of IFN-I and\n Chlamydia<\/jats:italic>\n resulted in a stronger induction of inflammation than\n Chlamydia<\/jats:italic>\n alone, while IFN-I alone had no effect. Inhibiting AKT and mTOR, but not silencing\n STAT1<\/jats:italic>\n , significantly attenuated the synergistic effect between IFN-I and bacteria on inflammation. Inhibition of ERK also blocked this synergistic effect, although ERK was not activated by IFN-I. We hypothesized that IFN-I enhanced the expression of a pathogen recognition receptor of the host, thereby potentiating detection of the bacteria and the subsequent inflammatory response. IFN-I, but not\n C. trachomatis<\/jats:italic>\n infection, increased the expression of Toll-like receptor 3 (TLR3), and silencing or knocking-out\n TLR3<\/jats:italic>\n prevented the synergistic effect between infection and IFN-I. Furthermore, our data support the presence of dsRNA in infected cells and the activation of the MAPK\/ERK and AP-1\/ATF2 signaling cascades downstream of TLR3. Taken together, our data demonstrate that IFN-I exacerbates the host inflammatory response triggered by\n Chlamydia<\/jats:italic>\n by increasing TLR3 expression and activation, leading to hyperinflammation. The identified signaling cascades represent potential targets for therapeutic intervention to limit tissue damage upon\n Chlamydia<\/jats:italic>\n infection.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n The effect of the production of IFN-I upon infection by\n Chlamydia trachomatis<\/jats:italic>\n is not well understood. We showed that IFN-I exacerbated\n Chlamydia<\/jats:italic>\n -induced inflammation in epithelial cells. This synergy was mediated by the IFN-induced upregulation of Toll-like receptor 3 (TLR3) expression, which facilitated sensing of\n Chlamydia<\/jats:italic>\n and amplified the inflammatory response. We identified the signaling cascades involved upstream and downstream of TLR3 signaling. By exacerbating the pro-inflammatory response of epithelial cells, IFN-I might contribute to the hyperinflammation experienced by some individuals. The signaling pathways we uncovered can serve as a starting point for novel therapeutic strategies to alleviate tissue damage upon\n Chlamydia<\/jats:italic>\n infection.\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/mbio.00527-26","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:00:40Z","timestamp":1781524840000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["IFN-I exacerbates the inflammatory response of epithelial cells to\n Chlamydia trachomatis<\/i>\n infection by enhancing TLR3 expression"],"prefix":"10.1128","volume":"17","author":[{"given":"Chongfa","family":"Tang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0495fxg12","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, UMR3691 CNRS, Cellular biology of microbial infection","place":["Paris, France"]},{"name":"Sorbonne Universit\u00e9, Coll\u00e8ge doctoral","place":["Paris, France"]},{"id":[{"id":"https:\/\/ror.org\/01p5m7v59","id-type":"ROR","asserted-by":"publisher"}],"name":"National Vaccine and Serum Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Cai","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0495fxg12","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, UMR3691 CNRS, Cellular biology of microbial infection","place":["Paris, France"]},{"name":"Sorbonne Universit\u00e9, Coll\u00e8ge doctoral","place":["Paris, France"]},{"id":[{"id":"https:\/\/ror.org\/00qxm3x60","id-type":"ROR","asserted-by":"publisher"}],"name":"Lanzhou Institute of Biological Products","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Niragire","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0495fxg12","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, UMR3691 CNRS, Cellular biology of microbial infection","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e9lix V.","family":"Louchez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0495fxg12","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, UMR3691 CNRS, Cellular biology of microbial infection","place":["Paris, France"]},{"name":"Sorbonne Universit\u00e9, Coll\u00e8ge doctoral","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u00ebl Victoria","family":"Levy-Zauberman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00bea5h57","id-type":"ROR","asserted-by":"publisher"}],"name":"Service de Chirurgie Gyn\u00e9cologique, Institut Mutualiste Montsouris","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7481-4846","authenticated-orcid":true,"given":"Agathe","family":"Subtil","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0495fxg12","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, UMR3691 CNRS, Cellular biology of microbial infection","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0050-8480","authenticated-orcid":true,"given":"Yongzheng","family":"Wu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0495fxg12","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, UMR3691 CNRS, Cellular biology of microbial infection","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-022-01177-x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.6187"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05549-11"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535152"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00686.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.1989.054.01.003"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-14-50"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119136"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-85123-7"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2017.03.008"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3787"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2021.01.007"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.02.003"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M604638200"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.2.1266"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.3.1291-1297.2004"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.45.1.62-66.1984"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.52.3.828-833.1986"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01525-06"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09144-7"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.11.7186"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00140-11"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1086\/367962"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.2220\/biomedres.26.179"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.11.6982"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00629-08"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz087"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701658"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.143"},{"key":"e_1_3_3_31_2","first-page":"141","article-title":"Comprehensive and definitive molecular cytogenetic characterization of HeLa cells by spectral karyotyping","volume":"59","author":"Macville M","year":"1999","unstructured":"Macville M, Schr\u00f6ck E, Padilla-Nash H, Keck C, Ghadimi BM, Zimonjic D, Popescu N, Ried T. 1999. Comprehensive and definitive molecular cytogenetic characterization of HeLa cells by spectral karyotyping. Cancer Res 59:141\u2013150.","journal-title":"Cancer Res"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057090"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0147-619x(90)90033-9"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780471729259.mc11a01s00"},{"key":"e_1_3_3_35_2","first-page":"201","article-title":"Stronger growth-inhibitory effect of interferon (IFN)-beta compared to IFN-alpha is mediated by IFN signaling pathway in hepatocellular carcinoma cells","volume":"30","author":"Damdinsuren B","year":"2007","unstructured":"Damdinsuren B, Nagano H, Wada H, Kondo M, Ota H, Nakamura M, Noda T, Natsag J, Yamamoto H, Doki Y, et al.. 2007. Stronger growth-inhibitory effect of interferon (IFN)-beta compared to IFN-alpha is mediated by IFN signaling pathway in hepatocellular carcinoma cells. Int J Oncol 30:201\u2013208.","journal-title":"Int J Oncol"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1002550"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-00805-8"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.12552"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-019-0147-5"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-01018-x"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/35099560"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019102166"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1033601"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00357-F"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.10.7395"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900301200"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401850"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.5402\/2012\/642141"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/34956"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02401-24"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2019.04.003"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00279434"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1251135"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09247"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc6027"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00296"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.23812\/20-80-A-29"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.3.1212"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0248-8663(02)00659-8"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26765-y"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01834-24"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.7.4289"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.125"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00483-19"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001548"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608393104"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.11.6545"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310175200"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20131492"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.12.016"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.08.031"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.056"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.02.004"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.00527-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.00527-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T13:03:30Z","timestamp":1783515810000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.00527-26"}},"subtitle":[],"editor":[{"given":"Carolyn B.","family":"Coyne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":73,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7,8]]}},"alternative-id":["10.1128\/mbio.00527-26"],"URL":"https:\/\/doi.org\/10.1128\/mbio.00527-26","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]},"assertion":[{"value":"2026-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00527-26"}}