{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:57:38Z","timestamp":1790402258351,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012276","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000}}],"reference-count":84,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI180610"],"award-info":[{"award-number":["R21AI180610"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006939","name":"Emory University","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100006939","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Center for Georgia Clinical & Translational Science Alliance of the National Institutes of Health","award":["UL1TR002378"],"award-info":[{"award-number":["UL1TR002378"]}]},{"name":"Emory National Primate Research Center National Primate Research Cente","award":["ORIP\/OD P51OD011132"],"award-info":[{"award-number":["ORIP\/OD P51OD011132"]}]},{"name":"Pediatrics\/Winship Flow Cytometry Core of Winship Cancer Institute of Emory University","award":["P30CA138292"],"award-info":[{"award-number":["P30CA138292"]}]},{"DOI":"10.13039\/100012423","name":"Children's Healthcare of Atlanta","doi-asserted-by":"publisher","award":["P30CA138292"],"award-info":[{"award-number":["P30CA138292"]}],"id":[{"id":"10.13039\/100012423","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA138292"],"award-info":[{"award-number":["P30CA138292"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["Senior Research Career Scientist award"],"award-info":[{"award-number":["Senior Research Career Scientist award"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The menstrual cycle influences the risk of acquiring sexually transmitted infections (STIs), including those caused by the pathogen <jats:italic>Chlamydia trachomatis<\/jats:italic> (<jats:italic>C. trachomatis<\/jats:italic>). However, the underlying immune contributions are poorly defined. A mouse model simulating the repetitive immune-mediated process of menstruation could provide valuable insights into tissue-specific determinants of protection against chlamydial infection within the cervicovaginal and uterine mucosae of the female reproductive tract (FRT). Here, we used the pseudopregnancy approach for inducing menstruation in na\u00efve C57Bl\/6 mice and performed vaginal challenge with <jats:italic>Chlamydia muridarum<\/jats:italic> (<jats:italic>C. muridarum<\/jats:italic>) over the course of decidualization, endometrial tissue remodeling, and menstruation. This strategy identified that a time point over pseudopregnancy corresponding to the late luteal phase of the menstrual cycle correlated with reduced bacterial burden. By evaluating the early infection site following challenge at this time point, we found that a greater abundance of NK cell populations and proinflammatory signaling, including IFN\u03b3, were strongly correlated with protection. FRT immune profiling in uninfected mice over pseudopregnancy or in pig-tailed macaques over the menstrual cycle identified periodic NK cell infiltration into the cervicovaginal tissues and luminal surface occurring over a similar time frame. Notably, these cell populations were transcriptionally distinct and enriched for programs associated with NK cell effector functions. Depletion of FRT NK cells during the late luteal phase time frame resulted in a loss of protection, enabling productive infection following <jats:italic>C. muridarum<\/jats:italic> challenge. This study shows that the pseudopregnancy murine menstruation model recapitulates dynamic changes occurring in mucosal immune states throughout the FRT as a result of endometrial remodeling and identifies NK cell localization at the FRT barrier site of pathogen exposure as essential for immune protection against primary <jats:italic>C. muridarum<\/jats:italic> infection.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012276","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T17:42:41Z","timestamp":1749231761000},"page":"e1012276","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Murine modeling of menstruation identifies immune correlates of protection during Chlamydia muridarum challenge"],"prefix":"10.1371","volume":"21","author":[{"given":"Laurel A.","family":"Lawrence","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Elliott","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Vidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa S.","family":"Varughese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Rong Tiger","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thien Duy","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Roy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C.","family":"Tuske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anice C.","family":"Lowen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Scharer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Shafer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7237-1826","authenticated-orcid":true,"given":"Alison","family":"Swaims-Kohlmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ppat.1012276.ref001","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1186\/1471-2334-13-534","article-title":"Chlamydia prevalence in the general population: is there a sex difference? a systematic review","volume":"13","author":"PW Dielissen","year":"2013","journal-title":"BMC Infect Dis"},{"key":"ppat.1012276.ref002","first-page":"1","article-title":"Sexually transmitted diseases treatment guidelines, 2015","volume":"64","author":"Centers for Disease Control and Prevention","year":"2015","journal-title":"MMWR Recomm Rep"},{"issue":"6241","key":"ppat.1012276.ref003","doi-asserted-by":"crossref","DOI":"10.1126\/science.aaa8205","article-title":"VACCINES. A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells","volume":"348","author":"G Stary","year":"2015","journal-title":"Science"},{"issue":"9","key":"ppat.1012276.ref004","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1016\/j.immuni.2023.08.004","article-title":"Infection induces tissue-resident memory NK cells that safeguard tissue health","volume":"56","author":"IS Schuster","year":"2023","journal-title":"Immunity"},{"key":"ppat.1012276.ref005","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1146\/annurev-immunol-093019-112809","article-title":"Tissue-Resident Immune Cells in Humans","volume":"40","author":"JI Gray","year":"2022","journal-title":"Annu Rev Immunol"},{"key":"ppat.1012276.ref006","volume-title":"U. N. 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