{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:55:55Z","timestamp":1774594555020,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,24]]},"group-title":"Microbiology","reference-count":36,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Chlamydia trachomatis<\/jats:italic>\n                  infection of the female genital tract can result in severe reproductive sequelae, including pelvic inflammatory disease, tubal scarring, and infertility. Type I interferons have been implicated in both host defense and immunopathogenesis during chlamydial infection, with conflicting conclusions across experimental systems. However, the specific contributions of individual interferon subtypes remain poorly defined. Here, we examined the role of interferon beta (IFN-\u03b2) in regulating epithelial immune responses and intracellular bacterial development during\n                  <jats:italic>Chlamydia muridarum<\/jats:italic>\n                  infection.\n                <\/jats:p>\n                <jats:p>Using murine oviduct epithelial (OE) cell lines derived from wild-type, IFN\u03b2\u2013deficient, and Toll-like receptor 3 (TLR3)\u2013deficient mice, we demonstrate that IFN-\u03b2 is a critical epithelial-intrinsic mediator of host defense. Loss of IFN-\u03b2 led to dysregulation of genes associated with inflammation, immune regulation, and fibrosis, altered chlamydial inclusion morphology, enhanced expression of bacterial genes throughout the chlamydial developmental cycle, and increased chlamydial replication. Importantly, exogenous IFN-\u03b2 restored both immune mediator production and bacterial control during IFN\u03b2-deficiency. Parallel analyses revealed that TLR3 deficiency phenocopied IFN-\u03b2 loss, supporting a TLR3\u2013IFN-\u03b2 signaling axis that restricts chlamydial growth.<\/jats:p>\n                <jats:p>\n                  Consistent with these\n                  <jats:italic>in vitro<\/jats:italic>\n                  findings, IFN\u03b2-deficient mice exhibited enhanced bacterial burden during genital tract infection. Together, these data establish IFN-\u03b2 as a protective epithelial mediator during chlamydial infection and demonstrate that type I interferon responses are not functionally uniform. Our findings provide a mechanistic framework to reconcile the protective role of IFN-\u03b2 with reports of reduced pathology in interferon-\u03b1\/\u03b2 receptor-deficient models and highlight the importance of dissecting individual interferon pathways in chlamydial immunopathogenesis.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>\n                    Genital tract infection with\n                    <jats:italic>Chlamydia trachomatis<\/jats:italic>\n                    remains a leading cause of preventable infertility worldwide. Although type I interferons are widely viewed as contributors to chlamydial pathology, most studies have examined global interferon signaling rather than the roles of individual interferon subtypes. In this study, we demonstrate that interferon beta (IFN-\u03b2) plays a protective, epithelial-intrinsic role during chlamydial infection by restricting bacterial development and shaping local immune responses. These findings challenge the prevailing view that type I interferons are uniformly detrimental in this setting and reveal that distinct interferon subtypes can exert opposing effects on host defense and disease outcome. By defining a TLR3\u2013IFN-\u03b2 signaling axis that limits chlamydial replication, this work advances our understanding of epithelial immunity in the female genital tract and has important implications for the design of targeted immunomodulatory strategies to prevent chlamydia-induced reproductive pathology.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.23.713660","type":"posted-content","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T15:00:53Z","timestamp":1774364453000},"source":"Crossref","is-referenced-by-count":0,"title":["Examining the impact of the\n                  <i>Chlamydia muridarum<\/i>\n                  -induced synthesis of IFN-\u03b2 during genital tract infection\n                  <sup>1<\/sup>"],"prefix":"10.64898","author":[{"given":"Ramesh","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iliana C.","family":"Cordova-Mendez","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Marian University-Wood College of Osteopathic Medicine Indianapolis, Indiana 46222"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fnu","family":"Litika","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Marian University-Wood College of Osteopathic Medicine Indianapolis, Indiana 46222"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan D.","family":"Kara","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Marian University-Wood College of Osteopathic Medicine Indianapolis, Indiana 46222"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rayna","family":"Moiz","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Butler University Indianapolis, Indiana 46268"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derrick","family":"Burgess","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Marian University-Wood College of Osteopathic Medicine Indianapolis, Indiana 46222"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arkaprabha","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Dept. of Microbiology; Indiana University School of Medicine Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8250-6261","authenticated-orcid":false,"given":"Wilbert A.","family":"Derbigny","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Marian University-Wood College of Osteopathic Medicine Indianapolis, Indiana 46222"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026032622251672000_2026.03.23.713660v1.1","first-page":"1","article-title":"Sexual and reproductive health of persons aged 10-24 years - United States, 2002-2007","volume":"58","author":"Centers for Disease C","year":"2009","journal-title":"MMWR Surveill Summ"},{"key":"2026032622251672000_2026.03.23.713660v1.2","first-page":"422","article-title":"Chlamydia trachomatis infection of the Fallopian tubes. 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Type I interferon signaling exacerbates Chlamydia muridarum genital infection in a murine model. J Immunol.","DOI":"10.1128\/IAI.00629-08"},{"key":"2026032622251672000_2026.03.23.713660v1.12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.3.2092"},{"key":"2026032622251672000_2026.03.23.713660v1.13","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00140-11"},{"key":"2026032622251672000_2026.03.23.713660v1.14","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01525-06"},{"key":"2026032622251672000_2026.03.23.713660v1.15","doi-asserted-by":"crossref","unstructured":"Derbigny WA , et al. 2012. Identifying a role for Toll-like receptor 3 in the innate immune response to Chlamydia muridarum infection in murine oviduct epithelial cells. 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Chlamydiae (Psittacosis-lymphogranuloma venereum-trachoma group). 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