FPR1は宿主免疫細胞のペスト受容体である
Patrick Osei-Owusu1,2, Thomas M Charlton1,2, Hwan Keun Kim1,2
1Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Lemont, IL, USA.
Nature
|September 20, 2019
まとめ
疫病菌 (Yersinia pestis) は,N型ペプチド受容体 (FPR1) を介して免疫細胞を標的とする特定のタンパク質 (LcrV) を使用する. FPR1を阻害したり変異させたりすると 宿主の防御に役割があることを示唆します
科学分野:
- 免疫学
- 微生物学
- 遺伝学
背景:
- イェルシニア・ペスティスは 免疫細胞を破壊することで 疫病を引き起こします
- この免疫細胞破壊を媒介する特定の宿主因は以前は知られていなかった.
研究 の 目的:
- 感染中に Y. pestis が標的となる宿主受容体を特定する.
- この受容体の疫病発生と宿主生存における役割を調査する.
主な方法:
- Y. pestis LcrVタンパク質とヒト免疫細胞の相互作用を調査した.
- Fpr1欠乏したマウスを利用して,生存率と疫病に対する免疫反応を評価した.
- FPR1の遺伝子変異を検診したヒト集団
主要な成果:
- LcrVはヒト免疫細胞のN型ペプチド受容体 (FPR1) に結合し,バクテリアのエフェクター伝達を促進する.
- Fpr1欠乏したマウスは,生存率とペストに対する保護性抗体反応が増加した.
- ヒトのFPR1変種 (FPR1R190W) が特定され,Y. pestisによる免疫細胞破壊に耐性を与えています.
結論:
- FPR1はマウスとヒトの両方でY.ペスティスの重要な受容体として作用する.
- FPR1欠乏症や特定の変異は,ペストに対する有意な保護を提供します.
- 疫病はおそらくFPR1アレルの進化に影響を与え,他の病気に対する人間の免疫に影響を与えた.
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