NLRP6炎症ゾームはリポテイコ酸を認識し,グラム陽性病原体感染を調節する
Hideki Hara1, Sergey S Seregin2, Dahai Yang1
1Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Cell
|November 6, 2018
まとめ
リポテヒオ酸 (LTA) はNLRP6炎症体を活性化し,先天的な免疫反応を起こす. この経路は,カスパース-11とインタールイキン-18 (IL-18) を含め,グラム陽性細菌感染症を悪化させる.
科学分野:
- 免疫学
- 微生物学
- 細胞生物学
背景:
- NLRP6炎症ゾームの活性化剤と機能は完全に理解されていません.
- グラム陽性細菌は,免疫調節効果が知られている成分であるリポテイコ酸 (LTA) を生成します.
研究 の 目的:
- NLRP6炎症体のアクティベーターを特定する.
- グラム陽性細菌感染症に対する先天的な免疫におけるNLRP6の役割を解明する.
主な方法:
- マクロファージにおけるNLRP6のLTA結合と活性化を研究した.
- Nlrp6ノックアウト (Nlrp6-/-) とCasp11ノックアウト (Casp11-/-) のマウスモデルを使用した.
- Listeria monocytogenes感染に対する感受性の評価と,サイトカインの産生を測定した.
主要な成果:
- リポテヒオ酸 (LTA) はNLRP6に直接結合して活性化します.
- NLRP6の活性化により,カスパーゼ-11とカスパーゼ-1が活性化され,IL- 1βとIL- 18の成熟が促進される.
- Nlrp6- / - と Casp11- / - のマウスは,L. monocytogenesの感染に対する感受性が低下し,病原体負荷が低く,IL-18の産生が低下しています.
- IL-18の投与は,Nlrp6-/- またはCasp11-/- のマウスの感受性を回復させる.
結論:
- NLRP6は,グラム陽性細菌の重要な成分である細胞性LTAによって活性化されます.
- このLTA-NLRP6-カスパース-11経路はIL-18の産生を促し,全身性グラム陽性細菌感染症を悪化させる.
- この発見は 宿主の防御と病原菌の制御に 欠かせない新しい 生まれながらの免疫経路を明らかにしています
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