The urokinase receptor can be induced by Borrelia burgdorferi through receptors of the innate immune system
The urokinase receptor can be induced by Borrelia burgdorferi through receptors of the innate immune system
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DOI：
10.1128/iai.71.10.5556-5564.2003
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发表时间：
2003-10-01
影响因子：
3.1
通讯作者：
Benach, JL
中科院分区：
文献类型：
--
作者：
Coleman, JL;Benach, JL
单核细胞暴露于伯氏疏螺旋体，通过未知的受体，过表达尿激酶受体（uPAR），纤溶酶原激活系统的关键介质。我们发现，联合阻断CD 14和TLR 2可显著抑制B。在Mono Mac 6（MM 6）细胞中，burgdorferi诱导的uPAR。检测的其他模式识别受体（CD 11 B/CD 18、甘露糖受体和N-甲酰基-甲硫氨酰亮氨酰-苯丙氨酸受体）未证实在B中的作用。burgdorferi介导的uPAR诱导。我们通过研究CD14和TLR2各自的奇异贡献来剖析结果。CD 14或TLR 2的独立功能性阻断不能抑制B。burgdorferi介导的uPAR诱导。1，25-二羟基维生素D-3诱导的MM 6细胞分化使CD 14表达增加12倍，但不增加B。burgdorferi介导的uPAR表达。CD 14或TLR 2缺陷小鼠的腹膜渗出液巨噬细胞（PEM）在B中没有缺陷。burgdorferi介导的uPAR mRNA和蛋白的合成。增加uPAR mRNA或蛋白质或两者都是明显的PEM从转基因和对照小鼠，即使在一个疏螺旋体螺旋体每细胞的比例。我们的结论是，信号uPAR反应，作为介导的B。burgdorferi，用CD14和TLR2作为部分贡献者进行。受CD14和TLR2控制的部分代表了宿主纤溶酶原激活和先天免疫系统之间的新联系。
Monocytic cells exposed to Borrelia burgdorferi, through unknown receptors, overexpress the urokinase receptor (uPAR), a key mediator of the plasminogen activation system. We show that combined blockade of CD14 and TLR2 causes a significant inhibition of B. burgdorferi-induced uPAR in Mono Mac 6 (MM6) cells. Other pattern recognition receptors tested (CD11b/CD18, the mannose receptor, and the N-formyl-methionylleucyl-phenylalanine receptor) did not have demonstrated roles in B. burgdorferi-mediated uPAR induction. We dissected the result for CD14 andTLR2 by investigating the singular contributions of each. Independent functional blockade of CD14 or TLR2 failed to inhibit B. burgdorferi-mediated uPAR induction. 1,25-Dihydroxyvitamin D-3 differentiation of MM6 cells increased CD14 expression 12-fold but did not augment B. burgdorferi-mediated uPAR expression. Peritoneal exudate macrophages (PEM) from CD14- or TLR2-deficient mice were not defective in B. burgdorferi-mediated synthesis of uPAR mRNA and protein. Increased uPAR mRNA or protein or both were apparent in PEM from transgenic and control mice, even at a ratio of one Borrelia spirochete per cell. We conclude that signaling for the uPAR response, as mediated by B. burgdorferi, proceeds with CD14 and TLR2 as partial contributors. That part under control of CD14 and TLR2 represents a new link between the host plasminogen activation and innate immunity systems.