CCR5は,Staphylococcus aureusの白毒素EDに対する受容体である
Francis Alonzo1, Lina Kozhaya, Stephen A Rawlings
1Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
Nature
|December 14, 2012
まとめ
Staphylococcus aureusの白血病毒素ED (LukED) は,CCR5受容体と結合することで免疫細胞を標的とする. マラビロクなどの薬でCCR5をブロックすると,S. aureusの毒性と感染を抑制する.
科学分野:
- 微生物学 微生物学とは
- 免疫学 免疫学とは
- 毒理学 毒理学 毒理学
背景:
- 毛穴を形成する毒素は,細菌の毒性の重要な要因である.
- Staphylococcus aureusは,白血病毒素を使用して宿主細胞,特に免疫細胞を殺します.
- stafilococcal leukotoxinsの特定の宿主標的は,ほとんど不明のままである.
研究 の 目的:
- レウコトキシン選択性を決定する宿主因子を特定するために.
- S. aureusの病原性における同定された因子の役割を調査する.
- この相互作用を標的とした治療戦略を探求する.
主な方法:
- 細胞ベースの測定法で,白血病毒素の細胞毒性を評価する.
- 遺伝的および生化学的アプローチを使用して宿主細胞受容体の識別.
- CCR5欠乏したマウスと感染モデルを用いたin vivo研究.
- CCR5アンタゴニストを用いた薬理学的抑制.
主要な成果:
- HIV共受容体CCR5は,S. aureusの白血病毒素ED (LukED) が骨髄細胞とTリンパ球を標的にする重要な決定因子として特定されています.
- HIV薬マラビロクを含むCCR5抗生物質は,LukED媒介による細胞破壊を効果的に阻害する.
- CCR5欠乏したマウスは,致命的なS. aureus感染に対する有意な耐性を示す.
- LukED媒介によるCCR5 (((+)) 白血球の枯渇は,新しい免疫回避戦略を表しています.
結論:
- CCR5は,S. aureus LukEDが免疫細胞を標的にするために利用する細胞受容体です.
- CCR5を標的にすることは,S. aureus感染症に対する潜在的な治療戦略を提供します.
- この相互作用を理解することで,細菌の免疫逃避の新たなメカニズムが明らかになる.
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