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

ABSTRACT: Interleukin-1β (IL-1β) production is impaired in cord blood monocytes. However, the mechanism underlying this developmental attenuation remains unclear. Here, we analyzed the extent of variability within the Toll-like receptor (TLR)/NLRP3 inflammasome pathways in human neonates. We show that immature low CD14 expressing/CD16(pos) monocytes predominate before 33 weeks of gestation, and that these cells lack production of the pro-IL-1β precursor protein upon LPS stimulation. In contrast, high levels of pro-IL-1β are produced within high CD14 expressing monocytes, although these cells are unable to secrete mature IL-1β. The lack of secreted IL-1β in these monocytes parallels a reduction of NLRP3 induction following TLR stimulation resulting in a lack of caspase-1 activity before 29 weeks of g

SUBMITTER: Sharma AA 

PROVIDER: S-EPMC4619041 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature