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RNA Sequencing Reveals Diverse Functions of Amniotic Fluid Neutrophils and Monocytes/Macrophages in Intra-Amniotic Infection
Journal of Innate Immunity ( IF 5.3 ) Pub Date : 2020-11-05 , DOI: 10.1159/000509718
Nardhy Gomez-Lopez 1, 2, 3 , Roberto Romero 4, 5, 6, 7, 8, 9 , Aneesha Varrey 4, 10 , Yaozhu Leng 4, 10 , Derek Miller 4, 10 , Bogdan Done 4, 10 , Yi Xu 4, 10 , Gaurav Bhatti 4, 10 , Kenichiro Motomura 4, 10 , Meyer Gershater 4, 10 , Roger Pique-Regi 4, 7, 10 , Adi L Tarca 4, 10, 11
Affiliation  

Intra-amniotic infection, the invasion of microbes into the amniotic cavity resulting in inflammation, is a clinical condition that can lead to adverse pregnancy outcomes for the mother and fetus as well as severe long-term neonatal morbidities. Despite much research focused on the consequences of intra-amniotic infection, there remains little knowledge about the innate immune cells that respond to invading microbes. We performed RNA-seq of sorted amniotic fluid neutrophils and monocytes/macrophages from women with intra-amniotic infection to determine the transcriptomic differences between these innate immune cells. Further, we sought to identify specific transcriptomic pathways that were significantly altered by the maternal or fetal origin of amniotic fluid neutrophils and monocytes/macrophages, the presence of a severe fetal inflammatory response, and pregnancy outcome (i.e., preterm or term delivery). We show that significant transcriptomic differences exist between amniotic fluid neutrophils and monocytes/macrophages from women with intra-amniotic infection, indicating the distinct roles these cells play. The transcriptome of amniotic fluid immune cells varies based on their maternal or fetal origin, and the significant transcriptomic differences between fetal and maternal monocytes/macrophages imply that those of fetal origin exhibit impaired functions. Notably, transcriptomic changes in amniotic fluid monocytes/macrophages suggest that these immune cells collaborate with neutrophils in the trafficking of fetal leukocytes throughout the umbilical cord (i.e., funisitis). Finally, amniotic fluid neutrophils and monocytes/macrophages from preterm deliveries display enhanced transcriptional activity compared to those from term deliveries, highlighting the protective role of these cells during this vulnerable period. Collectively, these findings demonstrate the underlying complexity of local innate immune responses in women with intra-amniotic infection and provide new insights into the functions of neutrophils and monocytes/macrophages in the amniotic cavity.
J Innate Immun


中文翻译:

RNA 测序揭示羊水中性粒细胞和单核细胞/巨噬细胞在羊膜内感染中的不同功能

羊膜内感染,微生物侵入羊膜腔导致炎症,是一种临床状况,可导致母亲和胎儿的不良妊娠结局以及严重的长期新生儿发病率。尽管很多研究都集中在羊膜内感染的后果上,但对对入侵微生物做出反应的先天免疫细胞知之甚少。我们对来自羊膜腔内感染女性的分选羊水中性粒细胞和单核细胞/巨噬细胞进行 RNA-seq,以确定这些先天免疫细胞之间的转录组差异。此外,我们试图确定特定的转录组学途径,这些途径被羊水中性粒细胞和单核细胞/巨噬细胞的母体或胎儿来源显着改变,严重胎儿炎症反应的存在和妊娠结果(即早产或足月分娩)。我们表明,羊水中性粒细胞和羊膜内感染女性的单核细胞/巨噬细胞之间存在显着的转录组学差异,表明这些细胞发挥了不同的作用。羊水免疫细胞的转录组因母体或胎儿来源而异,胎儿和母体单核细胞/巨噬细胞之间的显着转录组差异意味着胎儿来源的单核细胞/巨噬细胞表现出功能受损。值得注意的是,羊水单核细胞/巨噬细胞的转录组学变化表明,这些免疫细胞与中性粒细胞合作,在整个脐带中运输胎儿白细胞(即,脐炎)。最后,与足月分娩相比,来自早产的羊水中性粒细胞和单核细胞/巨噬细胞显示出增强的转录活性,突出了这些细胞在这个脆弱时期的保护作用。总的来说,这些发现证明了羊膜腔内感染女性局部先天免疫反应的潜在复杂性,并为羊膜腔中中性粒细胞和单核细胞/巨噬细胞的功能提供了新的见解。
J先天免疫
更新日期:2020-11-06
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