Environmental Toxicant Exposure Paralyzes Human Placental Macrophage Responses to Microbial Threat.
Victoria R StephensRebecca E MooreSabrina K SpicerJulie A TalbertJacky LuRiya ChinniSchuyler A ChambersSteven D TownsendShannon D ManningLisa M RogersDavid M AronoffZer VueKit NeikirkAntentor O HintonSteven M DamoKristen N NobleAlison J EastmanMonique M McCallisterKevin G OsteenJennifer A GaddyPublished in: ACS infectious diseases (2023)
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.
Keyphrases
- preterm birth
- endothelial cells
- adipose tissue
- oxidative stress
- immune response
- gene expression
- human health
- escherichia coli
- emergency department
- cell proliferation
- type diabetes
- risk assessment
- skeletal muscle
- insulin resistance
- cell cycle arrest
- low birth weight
- body mass index
- cell death
- single molecule
- cystic fibrosis
- staphylococcus aureus
- pi k akt
- adverse drug