トール型受容体2経路は,ヒトの微生物群の共生体によるコロニー化を確立する
June L Round1, S Melanie Lee, Jennifer Li
1Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. jround@caltech.edu
まとめ
腸内細菌のBacteroides fragilisは,そのポリサッカリドA (PSA) を使用して,T細胞のトール型受容体2 (TLR2) を活性化させ,免疫耐性を促進し,共生植民を促します. このメカニズムは,免疫系が有益な微生物と病原体を区別するのに役立ちます.
科学分野:
- 微生物学 微生物学とは
- 免疫学 免疫学とは
- 胃腸内科 胃腸内科
背景:
- 粘膜の表面は,多数の微生物と相互作用し,免疫認識機構を必要とします.
- トール型受容体 (TLR) は通常,病原体を排除するために微生物のパターンを識別します.
- 宿主-微生物の共生,特に腸内共生菌におけるTLRの役割は,活発な調査分野です.
研究 の 目的:
- 宿主-微生物共生における腸の共生性細菌 (Bacteroides fragilis) の役割を調査する.
- B. fragilisがトール型受容体 (TLR) 経路をどのように利用してコロニー化を確立するかを決定する.
- B. fragilisが免疫耐性を促進するメカニズムを解明する.
主な方法:
- マウスモデルを用いて,B. fragilisと宿主の免疫系との相互作用を研究した.
- TLR2シグナル伝達がCD4 (((+)) T細胞,特にFoxp3 (((+)) 調節性T細胞に与える役割を調査した.
- B. fragilisの重要な分子であるポリサッカリドA (PSA) のシンバイオシスを媒介する機能を調べました.
主要な成果:
- Bacteroides fragilisは,TLR経路,特にCD4 (((+)) T細胞のTLR2を活性化させ,ホメオスタシス中の独特の粘膜ニッチを植民地化します.
- B. fragilisの共生因子であるポリサッカリドA (PSA) は,Foxp3(+) 調節性T細胞にTLR2経由で信号を送り,免疫的耐性を誘発する.
- PSAが欠けているB. fragilis株は,Tヘルパー17細胞の反応を抑制できず,ニッチ固有のコロニー化に欠陥があった.
結論:
- B. fragilisのような共生細菌は,TLR経路を利用して主体の免疫を積極的に抑制し,共生関係を育むことができます.
- 免疫システムは,共生的な細菌分子を認識することによって,病原体と共生者を区別し,共生者の植民を容易にします.
- TLR2媒介によるPSAの認識は,腸内におけるB. fragilisの共生的なコロニー化にとって極めて重要です.
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