biostudies-literatureYang RFundamental Research Funds for the Central UniversitiesNatural Science Foundation of Hubei ProvinceChina Agricultural Research SystemChina Postdoctoral Science FoundationNational Natural Science Foundation of ChinaNational Key Research and Development Program of China988-999https://www.ebi.ac.uk/biostudies/studies/S-EPMC10928716biostudies-literatureUnknown10(3)<i>Escherichia coli</i> 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 <i>E. coli</i> meningitis. We observed that meningitic <i>E. coli</i> 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 <i>E. coli</i>-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 <i>E. coli</i> meningitis, thus eliciting the degradation of TJPs to induce BBB disruption. Our data indicated that IL-22 is an essential host accomplice during <i>E. coli</i>-caused BBB disruption and could be targeted for the therapy of bacterial meningitis.ACS infectious diseasesInterleukin-22 Contributes to Blood-Brain Barrier Disruption via STAT3/VEGFA Activation in <i>Escherichia coli</i> Meningitis.PMC109287162022M7212772021YFD18008002021CFA01632102749CARS-352662023PY005Liu HChen JTan CYang RQu XWang XChen HfalseInterleukin-22 Contributes to Blood-Brain Barrier Disruption via STAT3/VEGFA Activation in <i>Escherichia coli</i> Meningitis.<i>Escherichia coli</i> 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 <i>E. coli</i> meningitis. We observed that meningitic <i>E. coli</i> 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 <i>E. coli</i>-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 <i>E. coli</i> meningitis, thus eliciting the degradation of TJPs to induce BBB disruption. Our data indicated that IL-22 is an essential host accomplice during <i>E. coli</i>-caused BBB disruption and could be targeted for the therapy of bacterial meningitis.2024-01-01T00:00:00Z2024 Mar2025-04-19T05:51:32.022Z2025-04-19T05:51:32.022ZS-EPMC109287163831760710.1021/acsinfecdis.3c00668