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However, infections are commonly clinically asymptomatic and do not receive treatment. The underlying cause of asymptomatic immunopathology remains unknown. Here, we demonstrate that IgG produced during male infection enhanced the incidence of immunopathology and infertility in females. Human endocervical cells expressing the neonatal Fc Receptor (FcRn) increased translocation of human IgG\u2010opsonized <jats:italic>C.\u2009trachomatis<\/jats:italic>. Using total IgG purified from infected male mice, we opsonized <jats:italic>C.\u2009muridarum<\/jats:italic> and then infected female mice, mimicking sexual transmission. Following infection, IgG\u2010opsonized <jats:italic>Chlamydia<\/jats:italic> was found to transcytose the epithelial barrier in the uterus, where it was phagocytosed by antigen\u2010presenting cells (APCs) and trafficked to the draining lymph nodes. APCs then expanded both CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cell populations and caused significantly more infertility in female mice infected with non\u2010opsonized <jats:italic>Chlamydia<\/jats:italic>. Enhanced phagocytosis of IgG\u2010opsonized <jats:italic>Chlamydia<\/jats:italic> significantly increased pro\u2010inflammatory signalling and T cell proliferation. As IgG is transcytosed by FcRn, we utilized FcRn<jats:sup>\u2212\/\u2212<\/jats:sup> mice and observed that shedding kinetics of <jats:italic>Chlamydia<\/jats:italic> were only affected in FcRn<jats:sup>\u2212\/\u2212<\/jats:sup> mice infected with IgG\u2010opsonized <jats:italic>Chlamydia<\/jats:italic>. Depletion of CD8<jats:sup>+<\/jats:sup> T cells in FcRn<jats:sup>\u2212\/\u2212<\/jats:sup> mice lead to a significant reduction in the incidence of infertility. Taken together, these data demonstrate that IgG seroconversion during male infection can amplify female immunopathology, dependent on FcRn transcytosis, APC differentiation and enhanced CD8 T cell responses.<\/jats:p>","DOI":"10.1111\/sji.13331","type":"journal-article","created":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T06:39:28Z","timestamp":1697265568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>IgG<\/scp> exacerbates genital chlamydial pathology in females by enhancing pathogenic <scp>CD8<\/scp><sup>+<\/sup> T cell responses"],"prefix":"10.1111","volume":"99","author":[{"given":"Charles W.","family":"Armitage","sequence":"first","affiliation":[{"name":"Centre for Immunology and Infection Control and School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Connor P.","family":"O'Meara","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection Control and School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"},{"name":"Drop Bio Ltd, School of Biotechnology and Biomolecular Sciences (BABS) University of New South Wales  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8912-6878","authenticated-orcid":false,"given":"Emily R.","family":"Bryan","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection Control and School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avinash","family":"Kollipara","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection Control and School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Logan K.","family":"Trim","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection Control and School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danica","family":"Hickey","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection Control and School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison J.","family":"Carey","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection Control and School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilhelmina M.","family":"Huston","sequence":"additional","affiliation":[{"name":"School of Life Sciences University of Technology (UTS) Sydney  Ultimo New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Queensland Fertility Group (QFG)  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anusch","family":"Yazdani","sequence":"additional","affiliation":[{"name":"Queensland Fertility Group (QFG)  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard S.","family":"Blumberg","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine Brigham &amp; Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth W.","family":"Beagley","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection Control and School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"WHO.Sexually transmitted infections (STIs).Fact Sheets. 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