| First Author | He X | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 745854 | PubMed ID | 34721415 |
| Mgi Jnum | J:312725 | Mgi Id | MGI:6785485 |
| Doi | 10.3389/fimmu.2021.745854 | Citation | He X, et al. (2021) Endogenous alpha7 nAChR Agonist SLURP1 Facilitates Escherichia coli K1 Crossing the Blood-Brain Barrier. Front Immunol 12:745854 |
| abstractText | Alpha 7 nicotinic acetylcholine receptor (alpha7 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 alpha7 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 alpha7 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 alpha7 nAChR activation. Finally, the promoting effects of SLURP1 on the pathogenesis of E. coli K1 meningitis was significantly abolished in the alpha7 nAChR knockout mice. These results reveal that E. coli K1 exploits SLURP1 to activate alpha7 nAChR and facilitate its pathogenesis, and blocking SLURP1-alpha7 nAChR interaction might represent a novel therapeutic strategy for E. coli K1 meningitis. |
