{Reference Type}: Journal Article {Title}: Environmental Toxicant Exposure Paralyzes Human Placental Macrophage Responses to Microbial Threat. {Author}: Stephens VR;Moore RE;Spicer SK;Talbert JA;Lu J;Chinni R;Chambers SA;Townsend SD;Manning SD;Rogers LM;Aronoff DM;Vue Z;Neikirk K;Hinton AO;Damo SM;Noble KN;Eastman AJ;McCallister MM;Osteen KG;Gaddy JA; {Journal}: ACS Infect Dis {Volume}: 9 {Issue}: 12 {Year}: 2023 12 8 {Factor}: 5.578 {DOI}: 10.1021/acsinfecdis.3c00490 {Abstract}: Exposure to environmental toxicants (such as dioxins) has been epidemiologically linked to adverse reproductive health outcomes, including placental inflammation and preterm birth. However, the molecular underpinnings that govern these outcomes in gravid reproductive tissues remain largely unclear. Placental macrophages (also known as Hofbauer cells) are crucial innate immune cells that defend the gravid reproductive tract and help promote maternal-fetal tolerance. We hypothesized that exposure to environmental toxicants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could alter placental macrophage responses to inflammatory insults such as infection. To test this, placental macrophages were cultured in the presence or absence of TCDD and then infected with the perinatal pathogen Group B Streptococcus (GBS). Our results indicate that TCDD is lethal to placental macrophages at and above a 5 nM concentration and that sublethal dioxin exposure inhibits phagocytosis and cytokine production. Taken together, these results indicate that TCDD paralyzes placental macrophage responses to bacterial infection.