纽约大学医学院的研究人员完成的一项新研究表明,现有的HIV药物”马拉维若(maraviroc)”可能是治疗金黄色葡萄球菌感染的一个潜在的方法。

-2013年1月3日《自然》


中文翻译


【题目】CCR5是金黄色葡萄球菌白细胞毒素ED的受体

【译文】成孔毒素是许多病原细菌的重要毒力因子,也是金黄色葡萄球菌介导的杀伤宿主细胞的关键蛋白。金黄色葡萄球菌编码对中心粒细胞有毒性的成孔双组份白细胞毒素,但也可以特异性靶向其他免疫细胞。尽管自第一次描述葡萄球菌白细胞毒素活性已有数十年,但负责白细胞毒素对不同免疫细胞选择性的宿主因子尚不清楚。本研究确定人免疫缺陷病毒(HIV)供受体CCR5是一群髓细胞和T淋巴细胞通过金黄色葡萄球菌白细胞毒素ED(LukED)产生的细胞毒素靶向所必需的细胞决定因子。进一步证实LukED依赖的细胞杀伤作用可由CCR5受体拮抗剂所阻断,这些拮抗剂包括HIV药物马拉维若。很明显,CCR5缺陷小鼠很大程度对致命性金黄色葡萄球菌感染耐受,突出了CCR5靶向在金黄色葡萄球菌致病中的重要性。因此,LukED 导致的CCR5+白细胞的消除是金黄色葡萄球菌新的免疫逃逸机制,而这成为治疗靶点。 

英文原稿


[Title]: CCR5 is a receptor for Staphylococcus aureus leukotoxin ED

[Authors]:Francis Alonzo III,1 Lina Kozhaya,1, 5 Stephen A. Rawlings,1, 5 Tamara Reyes-Robles,1, 5 Ashley L. DuMont,1 David G. Myszka,4 Nathaniel R. Landau,1 Derya Unutmaz1, 2, 3 & Victor J. Torres1

[Abstract]Pore-forming toxins are critical virulence factors for many bacterial pathogens and are central to Staphylococcus aureus-mediated killing of host cells. S. aureus encodes pore-forming bi-component leukotoxins that are toxic towards neutrophils, but also specifically target other immune cells. Despite decades since the first description of staphylococcal leukocidal activity, the host factors responsible for the selectivity of leukotoxins towards different immune cells remain unknown. Here we identify the human immunodeficiency virus (HIV) co-receptor CCR5 as a cellular determinant required for cytotoxic targeting of subsets of myeloid cells and T lymphocytes by the S. aureus leukotoxin ED (LukED). We further demonstrate that LukED-dependent cell killing is blocked by CCR5 receptor antagonists, including the HIV drug maraviroc. Remarkably, CCR5-deficient mice are largely resistant to lethal S. aureus infection, highlighting the importance of CCR5 targeting in S. aureus pathogenesis. Thus, depletion of CCR5+ leukocytes by LukED suggests a new immune evasion mechanism of S. aureus that can be therapeutically targeted.

原文地址

http://www.nature.com/nature/journal/v493/n7430/full/nature11724.html

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