The Staphylococcal Toxin Panton-Valentine Leukocidin Targets Human C5a Receptors
The Staphylococcal Toxin Panton-Valentine Leukocidin Targets Human C5a Receptors
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DOI：
10.1016/j.chom.2013.04.006
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发表时间：
2013-05-15
影响因子：
30.3
通讯作者：
van Strijp, Jos A. G.
中科院分区：
文献类型：
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作者：
Spaan, Andras N.;Henry, Thomas;van Strijp, Jos A. G.
Panton-Valentine杀白细胞素（PVL）是一种与严重侵袭性感染相关的葡萄球菌双组分成孔毒素。PVL的靶细胞和种属特异性知之甚少，并且这种毒素在金黄色葡萄球菌毒力中的作用机制存在争议。在这里，我们确定了人类补体受体C5 aR和C5 L2作为PVL的宿主靶点，介导毒素结合和细胞毒性。C5 aR的表达和种间变异决定PVL的细胞和种特异性。C5 aR结合PVL组分LukS-PV是C5 a诱导的免疫细胞活化的有效抑制剂。这些发现提供了深入了解杀白细胞素的功能和葡萄球菌的毒力，并提供了方向，为今后的调查个人易感性严重的葡萄球菌疾病。
Panton-Valentine Leukocidin (PVL) is a staphylococcal bicomponent pore-forming toxin linked to severe invasive infections. Target-cell and species specificity of PVL are poorly understood, and the mechanism of action of this toxin in Staphylococcus aureus virulence is controversial. Here, we identify the human complement receptors C5aR and C5L2 as host targets of PVL, mediating both toxin binding and cytotoxicity. Expression and interspecies variations of the C5aR determine cell and species specificity of PVL. The C5aR binding PVL component, LukS-PV, is a potent inhibitor of C5a-induced immune cell activation. These findings provide insight into leukocidin function and staphylococcal virulence and offer directions for future investigations into individual susceptibility to severe staphylococcal disease.