哺乳類の細胞におけるFADDに依存する先天的な免疫機構

Siddharth Balachandran¹, Emmanuel Thomas, Glen N Barber

¹Department of Microbiology and Immunology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA.

Nature

|November 19, 2004

まとめ

FADDタンパク質が欠けている哺乳類の細胞は,抗ウイルス遺伝子発現が低下し,ウイルス感染症に敏感です. これはFADDを強調しています.

科学分野:

免疫学免疫学とは
ウイルス学ウイルス学ウイルス学
分子生物学は分子生物学である.

背景:

脊椎動物の先天免疫は,病原体に対する防御に不可欠です.
ウイルスの複製による二重鎖RNA (dsRNA) は,先天的な免疫反応を誘発する.
dsRNA媒介の抗ウイルス免疫におけるFADDの役割は完全に理解されていません.

研究の目的:

細胞内 dsRNA 活性化遺伝子発現における FADD の役割を調査する.
FADD媒介の抗ウイルス防御に関与するシグナル伝達経路を解明する.

主な方法:

FADDを欠く哺乳類の細胞における遺伝子発現の分析.
TLR3,PKR,RIPK1,TBK1,IRF-3を含むシグナリングコンポーネントの調査
ドロソフィラの先天的な免疫経路との比較.

主要な成果:

FADDが欠けている哺乳類の細胞は,タイプIインターフェロン生産を含む,欠陥のあるdsRNA活性化遺伝子発現を示します.
これらのFADD欠乏細胞は,ウイルス感染症に非常に敏感です.
FADD経路はTLR3とPKRとは独立しているが,RIPK1とTBK1によるIRF-3の活性化が必要である.

結論:

FADDは,哺乳類の細胞にI型インターフェロンやその他の抗ウイルス遺伝子を最適に誘導するために不可欠です.
保存されたFADD依存の病原体認識経路は,ドロソフィラに似た哺乳類に存在する.
この経路は,ウイルス病原体に対する効果的な宿主防御に不可欠です.

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