{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T06:31:30Z","timestamp":1786343490970,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Decidual macrophages (DMs) are strategically located at the maternal-fetal interface to orchestrate innate host defense while balancing tolerance to the allogenic fetus. An important pregnancy complication is chorioamnionitis characterized by infection\/inflammation in the fetal membranes and the amniotic fluid with upregulation of TNF\u03b1 and other pro-inflammatory cytokines. The goal of this study was to determine maternal vs fetal origin of DMs and to investigate whether TNF signaling play a role in DM response to chorioamnionitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Decidua tissue from pregnant Rhesus macaques given intraamniotic injection of lipopolysaccharide\/saline with or without the TNF inhibitor Adalimumab (n=33) and human subjects with\/out chorioamnionitis (n=11) were used for bulk RNAseq, scRNAseq, and flow cytometry experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In both human and Rhesus macaques, DMs coordinately upregulate both pro- and anti-inflammatory cytokines during chorioamnionitis. Although DMs did not express TNF during chorioamnionitis, inhibition of TNF signaling downregulated 50% of LPS induced genes. About 4% of the DMs were of male fetus origin. These fetal origin DMs selectively upregulated\n                      <jats:italic>IL6<\/jats:italic>\n                      mRNA during chorioamnionitis, suggesting a potential role in fetal immune priming.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>We suggest that DMs orchestrate a carefully balanced host defense with a restrained pro-inflammatory profile during chorioamnionitis to potentially prevent adverse outcomes while protecting the mother-fetus dyad. Activation of fetal origin macrophages during chorioamnionitis may have implications for shaping neonatal immune responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1858982","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T06:21:17Z","timestamp":1786342877000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Decidua macrophages display a restrained inflammatory profile during chorioamnionitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Neema","family":"Pithia","sequence":"first","affiliation":[{"name":"Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine, University of California","place":["Los Angeles, Los Angeles, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo V.","family":"Musumarra","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Life 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