Dual role of TLR4 in bacterial meningitis through regulating endothelial pyroptosis and inflammatory response during extraintestinal pathogenic <i>Escherichia coli</i> infection.

ABSTRACT: Bacterial meningitis is a severe central nervous system infection with incompletely understood pathogenesis. Here, we investigated the role of Toll-like receptor 4 (TLR4) in blood-brain barrier disruption induced by extraintestinal pathogenic Escherichia coli (ExPEC). In vitro studies revealed that ExPEC infection upregulated TLR4 expression in human brain microvascular endothelial cells and induced pyroptosis and tight junction protein degradation. TLR4 inhibition by TAK-242 significantly reduced pyroptosis and inflammatory responses but exacerbated tight junction disruption and bacterial invasion. In macrophages, TLR4 inhibition similarly attenuated pyroptosis and inflammatory responses. Interestingly, despite enhanced blood-brain barrier disruption and increased bacterial

SUBMITTER: Jia K 

PROVIDER: S-EPMC12353697 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature