細胞外M. tuberculosisのDNAは,宿主DNA感知経路を活性化することによって,オートファギーのためのバクテリアを標的とする
Robert O Watson1, Paolo S Manzanillo, Jeffery S Cox
1Department of Microbiology and Immunology, Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell
|August 21, 2012
まとめ
ユカリオット細胞はオートファギーを用いて,細胞性細菌を除去する. この研究では,Mycobacterium tuberculosisのDNAがどのようにウビキチンマーキングを誘発し,細菌がオートファゴソームに伝達し,感染に対する重要な先天性免疫につながるかを明らかにしています.
科学分野:
- 細胞生物学 細胞生物学
- 免疫学 免疫学とは
- 微生物学 微生物学とは
背景:
- ユカリオット細胞はオートファギーを用いて,細胞性病原体を除去する.
- オートファギーの誘導はマクロファージにおけるMycobacterium tuberculosisの複製を制限するが,その標的化メカニズムと自然感染における役割は不明である.
研究 の 目的:
- 宿主細胞内のMycobacterium tuberculosisを標的としたオートファギーのメカニズムを解明する.
- M. tuberculosisに対する先天的免疫における細胞性DNAセンシングとオートファギーの役割を調査する.
主な方法:
- バクテリアのESX-1分泌システムによるファゴソームの浸透性を研究した.
- バクテリアのユビキチン化のためのSTING依存型細胞溶解経路を利用した.
- オートファゴソーム配送におけるp62,NDP52,TBK1の役割を調べました.
- オートファギー経路が欠乏したマウスのM. tuberculosis感染に対する感受性の評価.
主要な成果:
- バクテリアのESX-1分泌システムは,ファゴソームの浸透を媒介し,M. tuberculosisへの細胞溶液のアクセスを可能にします.
- STING依存経路による細胞外細菌DNA認識は,細菌のユビキチン化に不可欠である.
- ユビキチン-オートファギーの受容体p62とNDP52は,キナーゼTBK1とともに,自己ファゴソームへのバクテリアの伝達を媒介する.
- バシリをオートファギーに運ぶ能力がないマウスは,M. tuberculosisの感染に極端に敏感である.
結論:
- M. tuberculosisとの闘いにおいて,DNAセンシング,先天的免疫,およびオートファギーの間の予期せぬ関連性を明らかにした.
- このオートファギーの経路は,M. tuberculosis感染に対する耐性において重要な役割を果たしていることが示されています.
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