単純ヘルペス脳炎の患者におけるTLR3欠乏症
Shen-Ying Zhang1, Emmanuelle Jouanguy, Sophie Ugolini
1Human Genetics of Infectious Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM), U550, Faculty Necker, Paris 75015, France.
Science (New York, N.Y.)
|September 18, 2007
まとめ
トール型受容体3 (TLR3) 遺伝子変異は,ヘルペス・シンプレックスウイルス1 (HSV-1) による小児脳炎を引き起こす. TLR3は,中枢神経系におけるHSV-1の制御に極めて重要であり,神経性ウイルスからの進化的圧力を示唆している.
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
- 遺伝学 遺伝学とは
背景:
- トールおよびトール型受容体 (TLRs) は,実験的な感染において免疫を付与することが知られている.
- 自然生態系における宿主防衛における彼らの役割は,ほとんど特徴づけられていないままである.
- ヘルペス・シンプレックスウイルス1 (HSV-1) の脳炎は,重度の神経疾患である.
研究 の 目的:
- ウイルス感染症,特にHSV-1に対する天然宿主防御におけるトール型受容体3 (TLR3) の役割を調査する.
- HSV-1脳炎に対する感受性に寄与する遺伝的要因を特定する.
主な方法:
- HSV-1脳炎と診断された子供の遺伝分析.
- 中枢神経系 (CNS) と外周細胞におけるTLR3の発現分析.
- ホスト防御におけるTLR3独立経路の評価.
主要な成果:
- HSV-1脳炎を患っている他の健康な子供では,支配的陰性TLR3アレルが特定されました.
- 中枢神経系におけるTLR3発現は,頭蓋骨神経経由で頭皮から脳へ広がるHSV-1を制御するために不可欠である.
- 皮質細胞と樹状細胞は,TLR3欠乏した個体において,HSV-1の封じ込めと他の病原体に対する防御のために,TLR3に依存しない経路を利用する.
結論:
- 人間のTLR3は,ほとんどの微生物に対する防御に多余的な役割を果たしますが,中枢神経系におけるHSV-1に対する自然な免疫には不可欠です.
- TLR3がHSV-1のようなニューロトロピックウイルスを制御する上で果たす重要な役割は,その進化的維持を促したのかもしれない.
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