Interleukin-22 Contributes to Blood–Brain Barrier Disruption via STAT3/VEGFA Activation in <i>Escherichia coli</i> Meningitis
Ruicheng Yang, Jiaqi Chen, Xinyi Qu, Hulin Liu, Xinyi Wang, Xinyi Wang, Chen Tan, Huanchun Chen, Xiangru Wang, Xiangru Wang
Abstract
High Resolution Image Download MS PowerPoint Slide Escherichia coli continues to be the predominant Gram-negative pathogen causing neonatal meningitis worldwide. Inflammatory mediators have been implicated in the pathogenesis of meningitis and are key therapeutic targets. The role of interleukin-22 (IL-22) in various diseases is diverse, with both protective and pathogenic effects. However, little is understood about the mechanisms underlying the damaging effects of IL-22 on the blood–brain barrier (BBB) in E. coli meningitis. We observed that meningitic E. coli infection induced IL-22 expression in the serum and brain of mice. The tight junction proteins (TJPs) components ZO-1, Occludin, and Claudin-5 were degraded in the mouse brain and human brain microvascular endothelial cells (hBMEC) following IL-22 administration. Moreover, the meningitic E. coli -caused increase in BBB permeability in wild-type mice was restored by knocking out IL-22. Mechanistically, IL-22 activated the STAT3-VEGFA signaling cascade in E. coli meningitis, thus eliciting the degradation of TJPs to induce BBB disruption. Our data indicated that IL-22 is an essential host accomplice during E. coli -caused BBB disruption and could be targeted for the therapy of bacterial meningitis.