Activation of brain endothelium by Escherichia coli K1 virulence factor cglD promotes polymorphonuclear leukocyte transendothelial migration

AbstractEscherichia coli K1 is the most common Gram-negative bacteria causing neonatal meningitis. Polymorphonuclear leukocyte (PMN) transmigration across the blood –brain barrier (BBB) is the hallmark of bacterial meningitis. Reportedly, the deletion of virulence factor cglD (E44:ΔcglD) from E44 is responsible for a less efficient PMN transendothelial migration ability. In the present study, we found that complementation of thecglD gene into E44: ΔcglD mutant strain might restore the PMN count and myeloperoxidase level in a neonatal mouse meningitis. Using human brain microvascular endothelial cells (HBMECs), the main model of the BBB in vitro, we found that E44: ΔcglD mutant strain induced a less efficient PMN adhesion to HBMECs and down-regulated chemokines CXCL1, CXCL6 and CXCL8 and adhesion molecule E-selectin, compared with the E44 strain. Complementation ofcglD restored the PMN adhesion to HBMECs and the level of these proteins. E44: ΔcglD mutant strain also induced a less efficient NF- κB pathway activation in HBMECs and reduced the soluble p65 (sp65) level in the cerebral spinal fluid of newborn mice, compared with the E44 strain. Complementation ofcglD restored the NF- κB pathway activation and increased the sp65 levels. This suggests thatcglD in E44 contributes to NF- κB pathway activation in the brain endothelium to promote PMN adhesion to HBMECs and transendothelial migration. Our identified novel requirement of cglD for immune activation and subsequent ...
Source: Medical Microbiology and Immunology - Category: Microbiology Source Type: research