ウイルス感染に対する自然抵抗性のコンメンサル微生物群の調節
Kailyn L Stefan1, Myoungjoo V Kim2, Akiko Iwasaki3
1Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Cell
|November 19, 2020
まとめ
腸内微生物,特に外膜のグリコリピドは,腸内におけるインターフェロン-β (IFN-β) の生成を誘導する. この微生物誘発IFN-βは天然の抗ウイルス免疫を強化し,潜在的な治療戦略を提供します.
科学分野:
- 免疫学
- 微生物学
- 分子生物学
背景:
- インターフェロン-I (IFN-I) は,抗ウイルス免疫と免疫システムのホメオスタシスに不可欠です.
- ホメオスタティック状態でのIFN-Iシグナリングの起源はほとんど不明である.
- 腸内微生物が宿主の免疫に 果たす役割はますます認識されています
研究 の 目的:
- ホメオスタティック条件下でIFN-I信号源を特定する.
- 交尾微生物がIFN-βを誘発するメカニズムを解明する.
- 微生物由来IFN-β誘発剤の治療の可能性を調査する.
主な方法:
- IFN- I応答における大腸の dendritic cells (DCs) の役割を調査した.
- バクテロイドス属の微生物からの外膜 (OM) 関連グリコリピドを使用した.
- 使われているバクテロイド・フレジリスとそのOM関連ポリサッカリドA (PSA)
- TLR4-TRIFを含む信号経路を分析した.
- 膀性口炎ウイルス (VSV) とインフルエンザに対する抗ウイルス作用を in vitro および in vivo で評価した (ネズミのモデル).
主要な成果:
- コンメンサルの微生物は,大腸のDCを通じてIFN-βの産生を誘導する.
- バクテロイド,特にB. fragilis PSAからの外膜グリコリピドは,TLR4-TRIFシグナル伝達を通じてIFN-β発現を活性化します.
- 精製された微生物分子はIFN-β誘導に依存する抗ウイルス活性を示した.
- コメンサル誘発のIFN-βは,ネズミのモデルでウイルスの感染に対する自然抵抗性を有意に調節した.
結論:
- 腸内共生微生物は,ホメオスタティックな条件下でIFN-βの重要な源である.
- 微生物のOM関連グリコリピドは,TLR4-TRIF経由でIFN-βを誘発する主要な因子である.
- 微生物のIFN-β誘導体の発見は,ウイルス性疾患に対する新しい治療法を示しています.
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