Streptococcus agalactiae Induces Placental Macrophages To Release Extracellular Traps Loaded with Tissue Remodeling Enzymes via an Oxidative Burst-Dependent Mechanism.
Streptococcus agalactiae Induces Placental Macrophages To Release Extracellular Traps Loaded with Tissue Remodeling Enzymes via an Oxidative Burst-Dependent Mechanism.
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DOI：
10.1128/mbio.02084-18
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发表时间：
2018-11-20
期刊：
影响因子：
6.4
通讯作者：
Gaddy JA
中科院分区：
文献类型：
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作者：
Doster RS;Sutton JA;Rogers LM;Aronoff DM;Gaddy JA
无乳链球菌，也被称为B群链球菌（GBS），是妊娠期间常见的病原体，感染可导致绒毛膜羊膜炎、早产、胎膜早破（PPROM）、早产、死产和新生儿败血症。GBS感染导致不良妊娠结局的机制仍不完全清楚。本研究评估了GBS与胎盘巨噬细胞之间的相互作用。数据表明，在对感染的反应中，胎盘巨噬细胞释放能够杀死GBS的细胞外陷阱。此外，这项工作还证实了与细胞外陷阱纤维相关的蛋白质包括几种与绒毛膜羊膜炎相关的基质金属蛋白酶。在怀孕的情况下，胎盘巨噬细胞对细菌感染的反应可能有有益和不利的后果，包括对细菌入侵的保护作用，但它们也可能释放重要的膜破坏介质，可能导致膜破裂或早产。无乳链球菌，或B族链球菌（GBS），是一种常见的围产期病原体。妊娠期阴道黏膜的GBS定植是侵袭性胎膜感染（绒毛膜羊膜炎）及其后果（如胎膜破裂、早产、死胎和新生儿败血症）的危险因素。胎盘巨噬细胞，或称霍夫鲍尔细胞，是存在于胎盘和胎膜组织中的来自胎儿的巨噬细胞，对胎儿和胎盘的发育起着至关重要的作用，包括支持血管生成、组织重塑和调节母胎耐受。虽然胎盘巨噬细胞作为组织内固有的吞噬细胞可能与侵袭性细菌（如GBS）发生接触，但关于这些细胞如何对细菌感染作出反应的信息有限。在这里，我们在体外证明胎盘巨噬细胞释放巨噬细胞细胞外陷阱（METs）以响应细菌感染。胎盘巨噬细胞METs含有蛋白质，包括组蛋白、髓过氧化物酶和中性粒细胞弹性酶，类似于中性粒细胞胞外陷阱，能够杀死GBS细胞。这些细胞释放MET的过程依赖于活性氧的产生。胎盘巨噬细胞METs还含有基质金属蛋白酶，在GBS反应中释放，可能导致感染期间胎膜变弱。在体外感染的人胎膜组织中发现了MET结构，这表明胎盘巨噬细胞在绒毛膜羊膜炎期间释放MET以响应细菌感染。
Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a common pathogen during pregnancy where infection can result in chorioamnionitis, preterm premature rupture of membranes (PPROM), preterm labor, stillbirth, and neonatal sepsis. Mechanisms by which GBS infection results in adverse pregnancy outcomes are still incompletely understood. This study evaluated interactions between GBS and placental macrophages. The data demonstrate that in response to infection, placental macrophages release extracellular traps capable of killing GBS. Additionally, this work establishes that proteins associated with extracellular trap fibers include several matrix metalloproteinases that have been associated with chorioamnionitis. In the context of pregnancy, placental macrophage responses to bacterial infection might have beneficial and adverse consequences, including protective effects against bacterial invasion, but they may also release important mediators of membrane breakdown that could contribute to membrane rupture or preterm labor. Streptococcus agalactiae, or group B Streptococcus (GBS), is a common perinatal pathogen. GBS colonization of the vaginal mucosa during pregnancy is a risk factor for invasive infection of the fetal membranes (chorioamnionitis) and its consequences such as membrane rupture, preterm labor, stillbirth, and neonatal sepsis. Placental macrophages, or Hofbauer cells, are fetally derived macrophages present within placental and fetal membrane tissues that perform vital functions for fetal and placental development, including supporting angiogenesis, tissue remodeling, and regulation of maternal-fetal tolerance. Although placental macrophages as tissue-resident innate phagocytes are likely to engage invasive bacteria such as GBS, there is limited information regarding how these cells respond to bacterial infection. Here, we demonstrate in vitro that placental macrophages release macrophage extracellular traps (METs) in response to bacterial infection. Placental macrophage METs contain proteins, including histones, myeloperoxidase, and neutrophil elastase similar to neutrophil extracellular traps, and are capable of killing GBS cells. MET release from these cells occurs by a process that depends on the production of reactive oxygen species. Placental macrophage METs also contain matrix metalloproteases that are released in response to GBS and could contribute to fetal membrane weakening during infection. MET structures were identified within human fetal membrane tissues infected ex vivo, suggesting that placental macrophages release METs in response to bacterial infection during chorioamnionitis.