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How the local milieu and constitutive stressors, including the cervicovaginal microbiota, shape the delicate balance underlying uterine immunity is poorly understood. Here, we found that the cervicovaginal microbiota promotes both local immunity and the immunoregulatory activity of interferon lambda (IFN-L) in the uterus. Using murine models, we found a keystone role for IFN-L in constraining the immune tone of this site, in particular of innate lymphoid cells and Th17 cells. Further, in the context of pregnancy, IFN-L enhanced antibacterial responses at maternal-fetal barriers to\n                  <jats:italic>Streptococcus agalactiae<\/jats:italic>\n                  infection, thereby controlling fetal and neonatal transmission. Collectively, this work uncovered how IFN-L integrates microbial signals under both steady state and pregnancy conditions and mediates the essential functions of the uterine immune system \u2013 antimicrobial protection and immunoregulation.\n                <\/jats:p>","DOI":"10.64898\/2026.01.27.701820","type":"posted-content","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T03:20:18Z","timestamp":1769743218000},"source":"Crossref","is-referenced-by-count":0,"title":["Microbiota-dependent IFN-L controls uterine and placental immunity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4840-113X","authenticated-orcid":false,"given":"Elisha","family":"Segrist","sequence":"first","affiliation":[{"name":"National Institute of General Medical Sciences, National Institutes of Health, Bethesda, MD 20892, USA"},{"name":"Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Roman","sequence":"additional","affiliation":[{"name":"HIV Pathogenesis Section, Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard","family":"Ansaldo","sequence":"additional","affiliation":[{"name":"Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Perez Chaparro","sequence":"additional","affiliation":[{"name":"NIAID Microbiome Program, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colton","family":"McNinch","sequence":"additional","affiliation":[{"name":"Science Support Section, Bioinformatics and Computational Bioscience Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irini","family":"Sereti","sequence":"additional","affiliation":[{"name":"HIV Pathogenesis Section, Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Belkaid","sequence":"additional","affiliation":[{"name":"Unite Metaorganisme, Immunology Department, Pasteur Institute, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026020511461979000_2026.01.27.701820v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3819"},{"key":"2026020511461979000_2026.01.27.701820v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2012.02.023"},{"issue":"2","key":"2026020511461979000_2026.01.27.701820v1.3","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41584-019-0351-2","article-title":"Immunological adaptations in pregnancy that modulate rheumatoid arthritis disease activity","volume":"16","year":"2020","journal-title":"Nature Reviews Rheumatology"},{"key":"2026020511461979000_2026.01.27.701820v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.04.008"},{"key":"2026020511461979000_2026.01.27.701820v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.01.013"},{"key":"2026020511461979000_2026.01.27.701820v1.6","doi-asserted-by":"crossref","first-page":"733619","DOI":"10.3389\/fcimb.2021.733619","article-title":"Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures","volume":"11","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"2026020511461979000_2026.01.27.701820v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.12.013"},{"key":"2026020511461979000_2026.01.27.701820v1.8","doi-asserted-by":"crossref","unstructured":"Anton, L. , et al., Cervicovaginal microbiome alters transcriptomic and epigenomic signatures across cervicovaginal epithelial barriers. 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