School of Veterinary and Life Sciences, Murdoch University, Murdoch, Australia.
School of Paediatrics and Child Health, University of Western Australia, Crawley, Australia.
J Leukoc Biol. 2017 Sep;102(3):645-656. doi: 10.1189/jlb.4RU0317-111R. Epub 2017 Jun 19.
The extreme vulnerability of preterm infants to invasive microbial infections has been attributed to "immature" innate immune defenses. Monocytes are important innate immune sentinel cells critical in the defense against infection in blood. They achieve this via diverse mechanisms that include pathogen recognition receptor- and inflammasome-mediated detection of microbes, migration into infected tissues, and differentiation into Mϕs and dendritic cells, initiation of the inflammatory cascade by free radicals and cytokine/chemokine production, pathogen clearance by phagocytosis and intracellular killing, and the removal of apoptotic cells. Relatively little is known about these cells in preterm infants, especially about how their phenotype adapts to changes in the microbial environment during the immediate postnatal period. Overall, preterm monocytes exhibit attenuated proinflammatory cytokine responses following stimulation by whole bacterial or specific microbial components in vitro. These attenuated cytokine responses cannot be explained by a lack of intracellular signaling events downstream of pattern recognition receptors. This hyporesponsiveness also contrasts with mature, term-like phagocytosis capabilities detectable even in the most premature infant. Finally, human data on the effects of fetal chorioamnionitis on monocyte biology are incomplete and inconsistent. In this review, we present an integrated view of human studies focused on monocyte functions in preterm infants. We discuss how a developmental immaturity of these cells may contribute to preterm infants' susceptibility to infections.
早产儿极易受到侵袭性微生物感染，这归因于其“不成熟”的固有免疫防御。单核细胞是固有免疫的重要哨兵细胞，在抵御血液感染中起着关键作用。它们通过多种机制实现这一目标，包括病原体识别受体和炎性小体介导的微生物检测、迁移到感染组织中、分化为 Mϕ 和树突状细胞、通过自由基和细胞因子/趋化因子产生启动炎症级联反应、吞噬和细胞内杀伤清除病原体，以及清除凋亡细胞。关于早产儿的这些细胞，人们知之甚少，尤其是它们的表型如何适应出生后即刻微生物环境的变化。总的来说，与成熟的足月婴儿相比，早产儿的单核细胞在体外受到全细菌或特定微生物成分刺激后，促炎细胞因子反应减弱。这些减弱的细胞因子反应不能用模式识别受体下游的细胞内信号事件缺乏来解释。这种低反应性也与即使在最早产儿中也能检测到的成熟、类似足月的吞噬能力形成对比。最后，关于胎儿绒毛膜羊膜炎对单核细胞生物学影响的人类数据并不完整和一致。在这篇综述中，我们提出了一个整合的观点，重点关注早产儿单核细胞的功能。我们讨论了这些细胞的发育不成熟如何导致早产儿易感染。
