Dendritic cell stimulation by mycobacterial Hsp70 is mediated through CCR5
Dendritic cell stimulation by mycobacterial Hsp70 is mediated through CCR5
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DOI：
10.1126/science.1133515
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发表时间：
2006-10-20
期刊：
影响因子：
56.9
通讯作者：
Lehner, Paul J.
中科院分区：
文献类型：
--
作者：
Floto, R. Andres;MacAry, Paul A.;Lehner, Paul J.
对分枝杆菌感染的有效宿主免疫应答必须在不诱导免疫病理学的情况下控制病原体传播。分枝杆菌热休克蛋白（myHsp70）的组成性过表达与受损的细菌持久性，但免疫介导的机制是未知的。我们发现，myHsp70，除了增强抗原递送到人树突状细胞，通过CCR5趋化因子受体信号，促进树突状细胞聚集，树突状细胞和T细胞之间的免疫突触形成，和效应免疫反应的产生。因此，CCR5作为myHsp70的模式识别受体，这可能对结核病的病理生理学和myHsps在肿瘤导向免疫治疗中的应用都有影响。
An effective host immune response to mycobacterial infection must control pathogen dissemination without inducing immunopathology. Constitutive overexpression of mycobacterial heat shock protein (myHsp70) is associated with impaired bacterial persistence, but the immune-mediated mechanisms are unknown. We found that myHsp70, in addition to enhancing antigen delivery to human dendritic cells, signaled through the CCR5 chemokine receptor, promoting dendritic cell aggregation, immune synapse formation between dendritic cells and T cells, and the generation of effector immune responses. Thus, CCR5 acts as a pattern-recognition receptor for myHsp70, which may have implications for both the pathophysiology of tuberculosis and the use of myHsps in tumor-directed immunotherapy.