Endogenous α7 nAChR Agonist SLURP1 Facilitates Escherichia coli K1 Crossing the Blood-Brain Barrier.
Endogenous α7 nAChR Agonist SLURP1 Facilitates Escherichia coli K1 Crossing the Blood-Brain Barrier.
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内源性 α7 nAChR 激动剂 SLURP1 促进大肠杆菌 K1 穿过血脑屏障
DOI：
10.3389/fimmu.2021.745854
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发表时间：
2021
影响因子：
7.3
通讯作者：
Huang SH
中科院分区：
文献类型：
--
作者：
He X;Wang L;Liu L;Gao J;Long B;Chi F;Hu T;Wan Y;Gong Z;Li L;Zhen P;Zhang T;Cao H;Huang SH
α 7烟碱乙酰胆碱受体（α7 nAChR）是大肠杆菌（Escherichia coli，E. coli）致病的关键因子。coli）K1脑膜炎是新生儿严重的中枢神经系统感染。然而，很少有人知道E。coli K1操纵α7 nAChR信号。在此，我们通过永生化细胞系、动物模型和人类转录分析，证明了E。coliK 1感染后可释放内源性α7 nAChR配体Ly 6/Plaur domain containing 1（SLURP 1）。SLURP 1的外源补充，结合SLURP 1敲低或过表达细胞系，表明SLURP 1是E.大肠杆菌K1侵袭和中性粒细胞迁移穿过血脑屏障（BBB）。此外，我们发现SLURP 1是E. coli K1诱导α7 nAChR活化。最后，研究了SLURP 1对大肠杆菌致病的促进作用。α7 nAChR基因敲除小鼠的大肠杆菌K1脑膜炎明显消失。这些结果表明，E. coli K1利用SLURP 1激活α7 nAChR并促进其致病，阻断SLURP 1-α7 nAChR相互作用可能是治疗大肠杆菌的新策略。大肠杆菌K1脑膜炎。
Alpha 7 nicotinic acetylcholine receptor (α7 nAChR) is critical for the pathogenesis of Escherichia coli (E. coli) K1 meningitis, a severe central nervous system infection of the neonates. However, little is known about how E. coli K1 manipulates α7 nAChR signaling. Here, through employing immortalized cell lines, animal models, and human transcriptional analysis, we showed that E. coli K1 infection triggers releasing of secreted Ly6/Plaur domain containing 1 (SLURP1), an endogenous α7 nAChR ligand. Exogenous supplement of SLURP1, combined with SLURP1 knockdown or overexpression cell lines, showed that SLURP1 is required for E. coli K1 invasion and neutrophils migrating across the blood-brain barrier (BBB). Furthermore, we found that SLURP1 is required for E. coli K1-induced α7 nAChR activation. Finally, the promoting effects of SLURP1 on the pathogenesis of E. coli K1 meningitis was significantly abolished in the α7 nAChR knockout mice. These results reveal that E. coli K1 exploits SLURP1 to activate α7 nAChR and facilitate its pathogenesis, and blocking SLURP1-α7 nAChR interaction might represent a novel therapeutic strategy for E. coli K1 meningitis.
二手烟雾暴露和儿童侵入性脑膜炎球菌疾病的风险：系统评价和荟萃分析。
影响因子：
4.5
作者：
Murray RL;Britton J;Leonardi-Bee J
通讯作者：
Leonardi-Bee J