科研之友
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摘要
Escherichia 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:cglD) from E44 is responsible for a less efficient PMN transendothelial migration ability. In the present study, we found that complementation of the cglD gene into E44:cglD 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:cglD 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 of cglD restored the PMN adhesion to HBMECs and the level of these proteins. E44:cglD mutant strain also induced a less efficient NF-B 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 of cglD restored the NF-B pathway activation and increased the sp65 levels. This suggests that cglD in E44 contributes to NF-B 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 PMN entry into the central nervous system suggests that therapies directed at neutralising this molecule will be beneficial in preventing bacterial meningitis progression.
- 出版日期2019-2
- 单位中国医科大学
