マクロファージにおけるトール型受容体シグナル伝達は,オートファージ経路とファゴサイトーシスを結びつける
Miguel A Sanjuan1, Christopher P Dillon, Stephen W G Tait
1Department of Immunology, St Jude Children's Research Institute, Memphis, Tennessee 38105, USA.
Nature
|December 22, 2007
まとめ
トール型受容体 (TLR) 信号伝達は,マクロファージにおけるファゴサイトーシスとオートファギーを結びつける. これは,ファゴソーム-ライソソーム融合と微生物の殺戮を強化し,病原体に対する先天的な免疫反応を改善します.
科学分野:
- 免疫学 免疫学とは
- 細胞生物学 細胞生物学
背景:
- ファゴサイトーシスは細胞外生物を除去し,オートファギーは細胞内生物を分解する.
- オートファギーは,二重膜のオートファゴソームがリソソームと融合することを意味します.
- トール型受容体 (TLR) のエンゲージメントは,ファゴサイト防御とオートファギーを活性化します.
研究 の 目的:
- TLRシグナリングがファゴシトーシスとオートファギーを結び付け,ファゴソーム機能を強化するかどうかを調査する.
主な方法:
- ネズミのマクロファージは,ファゴシトーシス中にTLRを誘発する粒子に曝された.
- オートファギータンパク質 (LC3,ベクリン1) とキナーゼの活性によるファゴソームへの誘導を評価した.
- ファゴソーム-リゾソーム融合と微生物殺戮を測定した.
主要な成果:
- TLRの関与は,ATG5とATG7.7に依存するファゴソームにLC3を迅速に勧誘した.
- ベクリン1とフォスホイノシチド-3-OHキナーゼの活性がLC3の採用に先行した.
- ファゴソームは,ライソソームとの融合,酸性化,微生物の破壊が強化されたことを示した.
結論:
- TLRシグナリングは,ファゴサイトーシスとオートファギーの経路を統合します.
- この統合は,ファゴソームの成熟と病原体のクリアランスを改善することによって,先天的な免疫を強化します.
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