Prenatal inflammation suppresses blood Th1 polarization and gene clusters related to cellular energy metabolism in preterm newborns

文献类型： 外文期刊

第一作者： Ren, Shuqiang

作者： Ren, Shuqiang;Pan, Xiaoyu;Gao, Fei;Sangild, Per T.;Nguyen, Duc Ninh;Gao, Fei;Sangild, Per T.;Sangild, Per T.

作者机构：

关键词： chorioamnionitis; immune development; lipopolysaccharide; neonatal sepsis; preterm infants

期刊名称：FASEB JOURNAL （ 影响因子：5.191； 五年影响因子：5.955 ）

ISSN： 0892-6638

年卷期： 2020 年 34 卷 2 期

页码：

收录情况： SCI

摘要： Chorioamnionitis (CA, fetal membrane inflammation) predisposes to preterm birth and is associated with increased neonatal infection risk, but the separate effects of prematurity, CA, and postnatal adaptations on this risk are unclear. Using pigs as models for infants, we examined the systemic immune-metabolic status in cesarean-delivered preterm pigs, with and without CA induced by intra-amniotic (IA) LPS exposure. At birth, cord blood of preterm pigs showed neutropenia and low expressions of innate and adaptive immune genes, relative to term pigs. IA LPS induced CA and fetal systemic innate immune activation via complement and neutrophil-related pathways. These were mainly modulated via cellular regulations rather than granulopoiesis, as validated by the in vitro LPS stimulation of cord blood. After birth, IA LPS-exposed preterm pigs did not follow normal immune-metabolic ontogenies found in fetuses or newborns without prenatal insults, but showed consistently high levels of Treg, impaired Th1 polarization, and reduced expressions of multiple genes related to cellular oxidative phosphorylation and ribosomal activities. In conclusion, our results provide cellular and molecular evidence for CA-induced distinct neonatal immune-metabolic status with increased disease tolerance strategy, suggesting mechanisms for the clinical observation of elevated sepsis risks in immune-compromised preterm infants born with CA.

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