細菌は脳内神経免疫軸を乗っ取り,脳への侵入を容易にする

Felipe A Pinho-Ribeiro^1,2, Liwen Deng¹, Dylan V Neel¹

¹Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.

Nature

|March 1, 2023

まとめ

細菌は痛みの経路を利用して髄膜炎を悪化させますこの経路を標的にすると免疫防御と脳と脳膜の細菌除去が強化され新たな治療法が生まれます

科学分野:

神経科学
免疫学
感染症

背景:

脳膜には痛みを感知する神経細胞 (ノシセプター) が豊富に含まれています
バクテリア性髄膜炎は重度の中枢神経系感染症で毎年何百万人にも影響します
痛みのシグナル伝達と神経免疫相互作用が,細菌に対する髄膜の防御における役割は,十分に理解されていません.

研究の目的:

細菌性髄膜炎における神経免疫軸を研究する
感染中にノシセプターと神経ペプチドが宿主の防御にどのように影響するか判断する.
この軸内の潜在的な治療目標を探求する.

主な方法:

細菌性髄膜炎のマウスモデルにおけるノシセプター神経の消去
細菌による病原体侵入 (Streptococcus pneumoniae,Streptococcus agalactiae) の分析
免疫細胞機能におけるカルシトニン遺伝子関連ペプチド (CGRP) とその受容体RAMP1の役割を調査した.

主要な成果:

ノシセプターニューロンの切除は髄膜と脳への細菌の侵入を大幅に減少させました
ストレプトコックスの肺毒素はノシセプターを活性化し,CGRPの放出につながります.
マクロファージのRAMP1経由でのCGRPシグナル伝達は,ケモカイン発現と中性粒子の増殖を含む免疫反応を抑制した.
RAMP1を阻害することで,細菌のクリアランスと免疫細胞の活性が強化された.

結論:

細菌は侵入を促進するために髄膜マクロファージの CGRP-RAMP1神経免疫軸をハイジャックします
この軸は細菌性髄膜炎に対する主体の防御を阻害します
この神経免疫経路をターゲットにすることで髄膜炎の治療を強化する潜在的治療戦略を提示します

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