{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:16:30Z","timestamp":1791594990577,"version":"4.3.4"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15AI117632, RO3AI128050"],"award-info":[{"award-number":["R15AI117632, RO3AI128050"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Genital <jats:italic>Chlamydia<\/jats:italic> is the most common bacterial sexually transmitted infection in the United States and worldwide. Previous studies indicate that the progression of chlamydial infection is influenced by various factors, including the female sex hormones estrogen and progesterone. Sex hormone levels naturally fluctuate in women throughout their menstrual cycle. Varying concentrations of estrogen and progesterone may impact the progression of chlamydial infection and the host\u2019s immune response to <jats:italic>Chlamydia<\/jats:italic>. Estrogen signals through estrogen receptors (ERs), ER\u03b1 and ER\u03b2. These receptors are similar in structure and function, but are differentially expressed in tissues throughout the body, including the genital tract and on cells of the immune system. In this study, we used ovariectomized (OVT) BALB\/c mice to investigate the impact of long-term administration of physiologically relevant concentrations of estrogen (E2), progesterone (P4), or a combination of E2\/P4 on the progression of and immune response to <jats:italic>C. muridarum<\/jats:italic> infection. Additionally, we used ER\u03b1 and ER\u03b2 knockout C57\/BL6 mice to determine the how ERs affect chlamydial infection and the resulting immune response. Estrogen exposure prevented <jats:italic>C. muridarum<\/jats:italic> infection in vaginally infected OVT mice exposed to E2 alone or in combination with P4, while OVT or Sham mice exposed to hormone free, P4 or depo-medroxyprogesterone acetate shed similar amounts of chlamydiae. The hormonal environment also altered T cell recruitment and IFN\u03f5 production the genital tracts of infected OVT and Sham mice on day 10 post infection. The absence of ER\u03b1, but not ER\u03b2, in ER knockout mouse strains significantly changed the timing of <jats:italic>C. muridarum<\/jats:italic> infection. ER\u03b1KO mice shed significantly more chlamydiae at day 3 post infection and resolved the infection faster than WT or ER\u03b2KO animals. At day 9 post infection, flow cytometry showed that ER\u03b1KO mice had more T cells present and targeted RNA sequencing revealed increased expression of <jats:italic>CD4<\/jats:italic> and <jats:italic>FOXP3<\/jats:italic>, suggesting that ER\u03b1KO mice had increased numbers of regulatory T cells compared to ER\u03b2KO and WT mice. Mock and chlamydia-infected ER\u03b1KO mice also expressed more IFN\u03f5 early during infection. Overall, the data from these studies indicate that sex hormones and their receptors, particularly ER\u03b1 and ER\u03b2, differentially affect <jats:italic>C. muridarum<\/jats:italic> infection in murine models of infection.<\/jats:p>","DOI":"10.3389\/fcimb.2022.939944","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T11:51:06Z","timestamp":1672141866000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["The hormonal environment and estrogen receptor signaling alters Chlamydia muridarum infection in vivo"],"prefix":"10.3389","volume":"12","author":[{"given":"Amy","family":"Gravitte","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Kintner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Cobble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Kennard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer V.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1080\/09674845.2013.11669935","article-title":"Chlamydia trachomatis: TLR4-mediated recognition by human dendritic cells is impaired following oestradiol treatment","volume":"70","author":"Agrawal","year":"2013","journal-title":"Br. 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