Nyarko E, Grab D J, Dumler J S
Division of Infectious Diseases, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Int J Parasitol. 2006 May 1;36(5):601-5. doi: 10.1016/j.ijpara.2006.01.014. Epub 2006 Mar 6.
The manifestations of Lyme disease, caused by Ixodes spp. tick-transmitted Borrelia burgdorferi, range from skin infection to bloodstream invasion into the heart, joints and nervous system. The febrile infection human granulocytic anaplasmosis is caused by a neutrophilic rickettsia called Anaplasma phagocytophilum, also transmitted by Ixodes ticks. Previous studies suggest that co-infection with A. phagocytophilum contributes to increased spirochetal loads and severity of Lyme disease. However, a common link between these tick-transmitted pathogens is dissemination into blood or tissues through blood vessels. Preliminary studies show that B. burgdorferi binds and passes through endothelial barriers in part mediated by host matrix metalloproteases. Since neutrophils infected by A. phagocytophilum are activated to release bioactive metalloproteases and chemokines, we examined the enhanced B. burgdorferi transmigration through vascular barriers with co-infection in vitro. To test whether endothelial transmigration is enhanced with co-infection, B. burgdorferi and A. phagocytophilum-infected neutrophils were co-incubated with EA.hy926 cells (HUVEC-derived) and human brain microvascular endothelial cells in Transwell cultures. Transmigration of B. burgdorferi through endothelial cell barriers was determined and endothelial barrier integrity was measured by transendothelial electrical resistivity. More B. burgdorferi crossed both human BMEC and EA.hy926 cells in the presence of A. phagocytophilum-infected neutrophils than with uninfected neutrophils without affecting endothelial cell integrity. Such a mechanism may contribute to increased blood and tissue spirochete loads.
由硬蜱属蜱虫传播的伯氏疏螺旋体引起的莱姆病，其表现范围从皮肤感染到血液传播至心脏、关节和神经系统。发热性感染人类粒细胞无形体病由一种名为嗜吞噬细胞无形体的嗜中性立克次体引起，同样也由硬蜱传播。先前的研究表明，与嗜吞噬细胞无形体共同感染会导致疏螺旋体负荷增加以及莱姆病病情加重。然而，这些蜱传播病原体之间的一个共同联系是通过血管扩散到血液或组织中。初步研究表明，伯氏疏螺旋体部分通过宿主基质金属蛋白酶介导与内皮屏障结合并穿过。由于被嗜吞噬细胞无形体感染的嗜中性粒细胞被激活以释放生物活性金属蛋白酶和趋化因子，我们在体外研究了共同感染时伯氏疏螺旋体通过血管屏障的迁移增强情况。为了测试共同感染是否会增强内皮迁移，将伯氏疏螺旋体和被嗜吞噬细胞无形体感染的嗜中性粒细胞与EA.hy926细胞（源自人脐静脉内皮细胞）和人脑微血管内皮细胞在Transwell培养体系中共孵育。测定伯氏疏螺旋体穿过内皮细胞屏障的迁移情况，并通过跨内皮电阻测量内皮屏障完整性。在存在被嗜吞噬细胞无形体感染的嗜中性粒细胞的情况下，穿过人脑血管内皮细胞和EA.hy926细胞的伯氏疏螺旋体比未感染的嗜中性粒细胞更多，且不影响内皮细胞完整性。这样一种机制可能导致血液和组织中疏螺旋体负荷增加。
