{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:49:20Z","timestamp":1792090160030,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014667","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000}}],"reference-count":126,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["309148\/Z\/24\/Z"],"award-info":[{"award-number":["309148\/Z\/24\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","award":["SBF009\/1079"],"award-info":[{"award-number":["SBF009\/1079"]}],"id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["228237\/Z\/23\/Z"],"award-info":[{"award-number":["228237\/Z\/23\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009187","name":"Medical Research Foundation","doi-asserted-by":"publisher","award":["MR\/Y00812\/1"],"award-info":[{"award-number":["MR\/Y00812\/1"]}],"id":[{"id":"10.13039\/501100009187","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Human African Trypanosomiasis (HAT) or sleeping sickness is a systemic parasitic infection caused by the protozoan parasite\n                    <jats:italic>Trypanosoma brucei.<\/jats:italic>\n                    HAT is associated with substantial immunological, metabolic, and neurological pathology. Although reproductive dysfunction has previously been recognised in both human and experimental\n                    <jats:italic>T. brucei<\/jats:italic>\n                    infection, whether parasites can directly infiltrate the female reproductive tract (FRT), and how infection may reshape the FRT immune landscape remains poorly understood. Using a murine model of\n                    <jats:italic>T. brucei<\/jats:italic>\n                    infection we reveal that parasites are localised in the uterine lining (endometrium) during both acute and chronic infection stages in mice. Chronic\n                    <jats:italic>T. brucei<\/jats:italic>\n                    infection was associated with progressive fat wasting, disruption of the reproductive (oestrous) cycle, uterine and ovarian atrophy, and extensive transcriptional dysregulation across the hypothalamic-pituitary-gonadal (HPG) axis. Acute and chronic infection induced remodelling of the uterine immune landscape, characterised by T cell infiltration, pro-inflammatory myeloid activation, alongside broader type 1 inflammatory changes across reproductive tissues and HPG components. Ovarian pathology was accompanied by follicular degeneration, a reduction in corpora lutea and alterations to steroidogenic pathways. Hormonal rescue with the selective oestrogen receptor modulator, tamoxifen, restored uterine morphology and prevented oestrous cycle arrest, but did not reverse the infection-induced uterine immune remodelling, indicating that endocrine dysfunction and infection-driven inflammation are distinct processes. Taken together, these findings identify the FRT as a major target of\n                    <jats:italic>T. brucei<\/jats:italic>\n                    infection and demonstrate how chronic parasitic infection can disrupt reproductive physiology through a combination of immune, endocrine, and metabolic pathways. They also highlight the need to specifically assess the FRT in other models of systemic inflammation.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014667","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:54:05Z","timestamp":1791568445000},"page":"e1014667","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trypanosoma brucei infection remodels the uterine immune environment and drives neuroendocrine dysfunction"],"prefix":"10.1371","volume":"22","author":[{"given":"Olivia M.","family":"Shorthouse","sequence":"first","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester","place":["Manchester, United Kingdom"]},{"name":"Division of Integrative Physiology, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester","place":["Manchester, United Kingdom"]},{"name":"Maternal and Foetal Health Research Centre, Division of Developmental Biology and Medicine, University of Manchester, St. Mary\u2019s Hospital","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Barnes","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester","place":["Manchester, United Kingdom"]},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-3437","authenticated-orcid":true,"given":"Stefano A. P.","family":"Colombo","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Costa","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester","place":["Manchester, United Kingdom"]},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrine","family":"Wonsbek","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester","place":["Manchester, United Kingdom"]},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anmoyul","family":"Mohon","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester","place":["Manchester, United Kingdom"]},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester","place":["Manchester, United Kingdom"]},{"name":"Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Mann","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester","place":["Manchester, United Kingdom"]},{"name":"Division of Integrative Physiology, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester","place":["Manchester, United Kingdom"]},{"name":"Maternal and Foetal Health Research Centre, Division of Developmental Biology and Medicine, University of Manchester, St. Mary\u2019s Hospital","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice H.","family":"Costain","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester","place":["Manchester, United Kingdom"]},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5092-5576","authenticated-orcid":true,"given":"Juan F.","family":"Quintana","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester","place":["Manchester, United Kingdom"]},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"issue":"8","key":"ppat.1014667.ref001","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.pt.2016.04.012","article-title":"Animal African trypanosomiasis: Time to increase focus on 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