細菌が分泌するタンパク質と宿主の上皮との相互作用によって結核性粒子の誘導
Hannah E Volkman1, Tamara C Pozos, John Zheng
1Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98155, USA.
Science (New York, N.Y.)
|December 17, 2009
まとめ
細菌を抑制すると考えられていた結核の粒腫は,実際には成長を促している. バクテリアのタンパク質ESAT-6はMMP9を誘発し,免疫細胞の徴募とミコバクテリアの増殖を促進し,MMP9を治療標的として示唆しています.
科学分野:
- 免疫学 免疫学とは
- 微生物学 微生物学とは
- 結核の病原性について
背景:
- グラヌロマは結核の特徴であり,Mycobacterium tuberculosisの成長を制限すると考えられていた.
- 最近の研究では,早期の粒腫は,新しい宿主細胞を徴募し,感染させることで,菌根菌の拡大を促進することが示唆されています.
研究 の 目的:
- マイコバクテリアが粒子の形成を誘発する分子機構を解明する.
- この過程における分泌タンパク質ESAT-6の役割を調査する.
- 結核治療のためにこのメカニズムを標的とする可能性を調査する.
主な方法:
- ゼブラフィッシュにおけるMycobacterium marinum感染モデルを活用した.
- ESAT-6によるマトリックスメタルプロテインアゼ-9 (MMP9) の誘導を上皮細胞で研究した.
- マクロファージの募集,花粉腫の成熟,バクテリアの成長に対するMMP9の影響を評価した.
- MMP9の機能障害は,小胞腫形成および細菌の増殖におけるその役割を評価する.
主要な成果:
- 隣接する上皮細胞でMMP9を誘発する重要な細菌因子としてESAT-6を特定した.
- MMP9が,感染していないマクロファージを花粉腫に勧誘することを強化することを実証した.
- MMP9が花粉腫の成熟に寄与し,菌根菌の成長を促進することを示した.
- MMP9の機能を妨害することで,粒子の形成とバクテリアの負荷が著しく低下することが判明しました.
結論:
- マイコバクテリアは,分泌されるタンパク質ESAT-6を利用して,上皮のMMP9を誘発し,それは花粉腫の形成と細菌の成長を促します.
- このメカニズムは,生産的な感染のために新しい宿主細胞の採用を伴う.
- エピテリアのMMP9生成をターゲットにすることは,結核に対する潜在的宿主指向の治療戦略を表しています.
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