Impaired NLRP3 inflammasome activity during fetal development regulates IL-1β production in human monocytes.

摘要: Interleukin-1β (IL-1β) production is impaired in cord blood monocytes. However, the mechanism underlying this developmental attenuation remains unclear. Here, we analyzed extent of variability within Toll-like receptor (TLR)/NLRP3 inflammasome pathways human neonates. We show that immature low CD14 expressing/CD16pos monocytes predominate before 33 weeks gestation, and these cells lack pro-IL-1β precursor protein upon LPS stimulation. In contrast, high levels are produced expressing monocytes, although unable to secrete mature IL-1β. The secreted IL-1β parallels a reduction NLRP3 induction following TLR stimulation resulting caspase-1 activity 29 whereas expression apoptosis-associated speck-like containing CARD function P2×7 preserved. Our analyses also reveal strong inhibitory effect placental infection on LPS/ATP-induced Lastly, secretion preterm neonates restored adult during neonatal period, indicating rapid maturation responses after birth. Collectively, our data highlight important mechanisms regulating early part due downregulation TLR-mediated expression. Such may serve limit potentially damaging inflammatory developing fetus.