肺における免疫の滅菌は,菌類のアポトーシスのようなプログラム細胞死を標的とする
Neta Shlezinger1, Henriette Irmer2, Sourabh Dhingra3
1Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
まとめ
肺中性粒子はアスペルギルス・コニディアのアポトーシスのような死を引き起こし,侵入性キノコ感染症を防ぐ. 抗アポプトシスタンパク質 AfBIR1は この一般的な菌類病原体に対する 免疫監視の重要な標的です
科学分野:
- 免疫学
- 菌類学
- 細胞生物学
背景:
- ヒトはしばしばカビのコニディアを吸い込み,通常は症状もなく除去します.
- 骨髄機能の欠陥は胞発芽と侵入性アスペルギロシスにつながるが,免疫監視メカニズムは完全に理解されていない.
研究 の 目的:
- 肺におけるアスペルギルス・コニディアに対する 骨髄細胞媒介免疫監視のメカニズムを調査する.
- ホストの免疫反応を回避するキノコの要因を特定する.
主な方法:
- ネズミの肺モデルにおける真菌生理学的インビオモニタリング
- アスペルギルス・フミガタスの遺伝子操作で AfBIR1 の役割が研究された.
- AfBIR1の活性に対する薬理学的抑制.
- NADPH酸化酵素依存殺菌に対するコンディアル感受性の評価
主要な成果:
- 肺中性粒子はアスペルギルス・コニディアのアポトーシスのような特徴を持つプログラム細胞死を誘発する.
- 抗アポプトシスタンパク質AfBIR1は,真菌のカスパース活性化とDNA断片化を阻害し,コニディアの生存を促進する.
- AfBIR1の発現と活動は,NADPH酸化因子による殺菌に対するコンディアル耐性と,侵入性アスペルギロシスの宿主感受性と相関する.
結論:
- ホストの免疫監視は,アスペルギルス・コニディアを制御するために,菌類のアポトーシスのようなプログラム細胞死経路を使用します.
- AfBIR1を標的にすることは,侵入性アスペルギロシスに対する宿主の免疫を強化するための潜在的な戦略です.
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