循環型AMPは,Mycobacterium tuberculosisのアデニラートサイクラースによるマクロファグの毒化を意味する
Nisheeth Agarwal1, Gyanu Lamichhane, Radhika Gupta
1Department of Medicine, Johns Hopkins School of Medicine, CRB2, Room 1.08, 1550 Orleans Street, Baltimore, Maryland 21231-1044, USA.
Nature
|June 12, 2009
まとめ
結核細菌は,特定の酵素 (Rv0386) を使用して,循環型AMP (cAMP) を宿主細胞に提供します. このバクテリアのcAMPは免疫信号伝達を妨害し,結核の生存と持続を助けます.
科学分野:
- 微生物学 微生物学とは
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
背景:
- 結核 (TB) は,毎年何百万もの死者を引き起こす世界的な健康上の大きな脅威であり続けています.
- 結核菌菌 (Mycobacterium tuberculosis,M.tb) は宿主マクロファージに感染し,その生存のために細胞環境を変更する.
- マイコバクテリア感染中にマクロファージで観察されるサイクルAMP (cAMP) 爆発の背後にあるメカニズムは完全に理解されていません.
研究 の 目的:
- M.tbのウイルス性におけるアデニラートサイクラース遺伝子の役割を調査する.
- 細菌由来のcAMPが宿主マクロファージに伝達されるメカニズムを解明する.
- 細菌のcAMPが宿主の免疫反応と細菌の生存にどのように影響するかを理解する.
主な方法:
- M.tbにおける17のアデニラートサイクラゼ遺伝子のウイルス性に対するスクリーニング.
- Rv0386の削除がマクロファージへのcAMP伝達に与える影響を評価する.
- TNF-αの産生,免疫病理学,細菌の生存に対する,縮小したマクロファージ内cAMPの影響を分析した.
主要な成果:
- M.tb.ウイルス性の重要なアデニラートサイクラゼ遺伝子としてRv0386を特定しました.
- Rv0386が,細菌のcAMPをマクロファージの細胞プラズマに伝達することを促進することを示した.
- Rv0386の喪失と,その後のマクロファージ内cAMPの減少は,TNF-αの産生,免疫病理,細菌の生存を低下させることを示した.
結論:
- Rv0386によって提供される細菌由来cAMPは,宿主の免疫応答を調節する上で重要な役割を果たします.
- M.tbは細菌のcAMPを利用して,その細胞内および組織環境を操作し,長期的な生存を促進します.
- バクテリアによるcAMPの投与をターゲットにすることは,結核の制御のための潜在的な戦略かもしれません.
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