Environmental Toxicant Exposure Paralyzes Human Placental Macrophage Responses to Microbial Threat
Year: 2023
Type: article
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.
Source: ACS Infectious Diseases
Authors: Victoria R. Stephens, Rebecca E. Moore, Sabrina K. Spicer, Julie A. Talbert, Jacky Lu, Riya Chinni, Schuyler A. Chambers, Steven D. Townsend, Shannon D. Manning, Lisa M. Rogers, David M. Aronoff, Zer Vue, Kit Neikirk, Antentor O. Hinton, Steven M. Damo, Kristen N. Noble, Alison J. Eastman, Monique M. McCallister, Kevin G. Osteen, Jennifer A. Gaddy
Institutions: Vanderbilt University Medical Center, Vanderbilt University, Children's Hospital Los Angeles, Stanford University, Michigan State University, Indiana University Indianapolis, Indiana University School of Medicine, Fisk University, Tennessee State University, Meharry Medical College, VA Tennessee Valley Healthcare System
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, U.S. Environmental Protection Agency, U.S. Department of Veterans Affairs, Burroughs Wellcome Fund, Alfred P. Sloan Foundation, Camille and Henry Dreyfus Foundation, Bristol-Myers Squibb, Vanderbilt University, Dartmouth College, Chan Zuckerberg Initiative, National Institutes of Health, Vanderbilt Diabetes Research and Training Center, Vanderbilt University Medical Center, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Institute of Child Health and Human Development, Division of Chemistry, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Division of Equity for Excellence in STEM, United Negro College Fund
Awards: G1110637377, G117257630, G1478761210, G1898711858, G2019238319, CREST: Center for Biological Signature and Sensing, G2165008609, Immunologic Contributions to the Endometriosis Phenotype, G2288832684, G2321377902, G2393974219, G2395189913, Pediatric Scientist Development Program, G2715995728, CAREER: Bioorganic Investigation of Human Milk Oligosaccharide Modulation of Group B Streptococcus, G2979489556, G3598735685, G381499422, G3964786795, G4731565586, G489658162, Training in Cardiovascular Research, G5232595009, G5239242941, G5656976469, Research Initiation Award: Revealing the Structural Basis for Calprotectin-RAGE Signaling Axis, PRIDE-Functional and Translational Genomics of Blood Disorders, G6141416877, G7089030656, Diabetes Research and Training Center, Probing the architecture, assembly, and function of amyloid-polysaccharide entanglements in bacterial biofilms, The Role of macrophages in chorioamnionitis and group B streptococcal infections, G8512132013, G9000003929, G9000004063, G9000052735, G9000206963, G9000339080, Vanderbilt Diabetes Research Center
OpenAlex ID: W4388632260