Analysis of the pathogenic mechanism of Shiga toxin-producing Escherichia coli infection for vaccine development

产志贺毒素（Stx）的大肠杆菌O157: H7感染蛋白质-卡路里营养不良小鼠可导致急性脑病；因此，受感染的动物在感染后10-12天内死亡。感染小鼠血清TNF-α水平在感染后2天升高，1或2天后血液中可检测到Stx。感染后第5天血清IL-10水平升高。在体外研究中，TNF-α加速了人脐静脉内皮细胞（HUVEC）对Stx的摄取，并加速了Stx在细胞内的活化，导致HUVEC细胞凋亡。首先将细胞暴露于TNF-α 6小时，然后与Stx孵育，这种凋亡诱导作用显著增强。IL-10减少TNF-α和Stx诱导的细胞凋亡。这些结果表明，Stx损伤暴露于循环TNF-α的血管内皮细胞，从而通过受损的血脑屏障进入大脑，血清IL-10可能保护血管内皮细胞的凋亡。

Shiga toxin (Stx)-producing Escherichia coli O157 : H7 infection in mice with protein-calorie-malnutrition leads to acute encephalopathy ; thereby, infected animals died within 10-12 days after infection. In infected mice, serum levels of TNF-α was increased 2 days after infection, 1 or 2 days after which Stx was detectable in the blood. Serum levels of IL-10 were also increased after day 5 of infection. In vitro studies, TNF-α accelerated the uptake of Stx by human umbilical venous endothelial cells (HUVEC) as well as the intracellular activation of Stx, which results in apoptosis in HUVEC. Such apoptosis induction was significantly enhanced by first exposing the cells to TNF-α for 6 h and subsequently by incubating them with Stx. IL-10 reduced the apoptosis induced by TNF-α and Stx. These results suggest that Stx damages vascular endothelial cells exposed to circulating TNF-α, thereby entering the brain through the damaged blood-brain barrier, and also that serum IL-10 may protect apoptosis in vascular endothelial cells.