Environmental Toxicant Exposure Paralyzes Human Placental Macrophage Responses to Microbial Threat
Environmental Toxicant Exposure Paralyzes Human Placental Macrophage Responses to Microbial Threat
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DOI：
10.1021/acsinfecdis.3c00490
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发表时间：
2023-11-13
影响因子：
5.3
通讯作者：
Gaddy，Jennifer A.
中科院分区：
文献类型：
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作者：
Stephens，Victoria R.;Moore，Rebecca E.;Gaddy，Jennifer A.
从流行病学角度来看，接触环境毒物（如二恶英）与不良生殖健康结果有关，包括胎盘炎症和早产。然而，在妊娠生殖组织中控制这些结果的分子基础仍然不清楚。胎盘巨噬细胞（也称为霍夫鲍尔细胞）是重要的先天免疫细胞，可保护妊娠生殖道并有助于促进母婴耐受。我们假设暴露于 2,3,7,8-四氯二苯并-对二恶英 (TCDD) 等环境毒物可能会改变胎盘巨噬细胞对感染等炎症损伤的反应。为了测试这一点，在存在或不存在 TCDD 的情况下培养胎盘巨噬细胞，然后用围产期病原体 B 组链球菌 (GBS) 进行感染。我们的结果表明，TCDD 在 5 nM 及以上浓度时对胎盘巨噬细胞是致命的，并且亚致死的二恶英暴露会抑制吞噬作用和细胞因子的产生。总而言之，这些结果表明 TCDD 麻痹胎盘巨噬细胞对细菌感染的反应。
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 BStreptococcus(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.