Increased levels of soluble CD40L in African tick bite fever:: Possible involvement of TLRs in the pathogenic interaction between Rickettsia africae, endothelial cells, and platelets
Increased levels of soluble CD40L in African tick bite fever:: Possible involvement of TLRs in the pathogenic interaction between Rickettsia africae, endothelial cells, and platelets
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DOI：
10.4049/jimmunol.177.4.2699
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发表时间：
2006-08-15
影响因子：
4.4
通讯作者：
Aukrust, Pal
中科院分区：
文献类型：
--
作者：
Damas, Jan K.;Jensenius, Mogens;Aukrust, Pal
斑点热群立克次体的病理生理特征是内皮细胞感染，随后炎症细胞浸润。基于CD40L促进炎症和内皮细胞激活的能力，我们使用不同的实验方法研究了CD40L在由非洲立克次体引起的非洲蜱咬伤热(ATBF)中的作用。有几个重要的发现被揭示出来。1)ATBF患者(n=15)血清可溶性CD40配体(SCD40L)水平升高，随访期下降。2)这些增强的sCD40L水平似乎反映了非洲锥虫对血小板的直接和间接影响(通过涉及CX3CL1相关机制的内皮细胞激活)。3)非洲分支杆菌与sCD40L结合，通过上调组织因子和下调血栓调节蛋白的表达，促进内皮细胞的促凝状态。4)尽管非洲支原体介导的血小板活化涉及TLR2，但非洲支原体和sCD40L对内皮细胞的联合促凝作用涉及TLR4。5)多西环素可拮抗非洲支原体和sCD40L对内皮细胞的联合促凝作用。我们的发现提示ATBF中血小板和内皮细胞之间存在炎性相互作用，涉及TLR相关机制。这种相互作用，包括sCD40L和非洲分支杆菌之间的相加作用，可能有助于这种疾病的内皮炎症和高凝状态。
The pathophysiological hallmark of spotted fever group rickettsioses comprises infection of endothelial cells with subsequent infiltration of inflammatory cells. Based on its ability to promote inflammation and endothelial cell activation, we investigated the role of CD40L in African tick bite fever (ATBF), caused by Rickettsia africae, using different experimental approaches. Several significant findings were revealed. 1) Patients with ATBF (n = 15) had increased serum levels of soluble CD40 ligand (sCD40L), which decreased during follow-up. 2) These enhanced sCD40L levels seem to reflect both direct and indirect (through endothelial cell activation involving CX3CL1-related mechanisms) effects of R. africae on platelets. 3) In combination with sCD40L, R. africae promoted a procoagulant state in endothelial cells by up-regulating tissue factor and down-regulating thrombomodulin expression. 4) Although the R. africae-mediated activation of platelets involved TLR2, the combined procoagulant effects of R. africae and sCD40L on endothelial cells involved TLR4. 5) Doxycycline counteracted the combined procoagulant effects of R. africae and sCD40L on endothelial cells. Our findings suggest an inflammatory interaction between platelets and endothelial cells in ATBF, involving TLR-related mechanisms. This interaction, which includes additive effects between sCD40L and R. africae, may contribute to endothelial inflammation and hypercoagulation in this disorder.