Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Detroit, MI and Bethesda, MD.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI.
J Immunol. 2024 Dec 1;213(11):1620-1634. doi: 10.4049/jimmunol.2400467.
Preterm birth (PTB), often preceded by preterm labor, is a major cause of neonatal morbidity and mortality worldwide. Most PTB cases involve intra-amniotic inflammation without detectable microorganisms, termed in utero sterile inflammation, for which there is no established treatment. In this study, we propose homeostatic macrophages to prevent PTB and adverse neonatal outcomes caused by in utero sterile inflammation. Single-cell atlases of the maternal-fetal interface revealed that homeostatic maternal macrophages are reduced with human labor. M2 macrophage treatment prevented PTB and reduced adverse neonatal outcomes in mice with in utero sterile inflammation. Specifically, M2 macrophages halted premature labor by suppressing inflammatory responses in the amniotic cavity, including inflammasome activation, and mitigated placental and offspring lung inflammation. Moreover, M2 macrophages boosted gut inflammation in neonates and improved their ability to fight systemic bacterial infections. Our findings show that M2 macrophages are a promising strategy to mitigate PTB and improve neonatal outcomes resulting from in utero sterile inflammation.
早产（PTB）常以前期早产为前驱，是全球新生儿发病率和死亡率的主要原因。大多数 PTB 病例涉及无明显微生物的羊膜内炎症，称为宫内无菌性炎症，目前尚无明确的治疗方法。在这项研究中，我们提出稳态巨噬细胞来预防宫内无菌性炎症引起的 PTB 和不良新生儿结局。母体-胎儿界面的单细胞图谱显示，随着人类分娩，稳态母巨噬细胞减少。M2 巨噬细胞治疗可预防宫内无菌性炎症小鼠的 PTB 并降低不良新生儿结局。具体而言，M2 巨噬细胞通过抑制羊膜腔中的炎症反应（包括炎症小体激活）来阻止早产，并减轻胎盘和后代肺部炎症。此外，M2 巨噬细胞增强了新生儿的肠道炎症，并提高了他们对抗全身细菌感染的能力。我们的研究结果表明，M2 巨噬细胞是一种有前途的策略，可以减轻 PTB 并改善宫内无菌性炎症引起的新生儿结局。
