Endogenous α7 nAChR Agonist SLURP1 Facilitates Escherichia coli K1 Crossing the Blood-Brain Barrier

Alpha 7 nicotinic acetylcholine receptor (alpha 7 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 alpha 7 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 alpha 7 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 alpha 7 nAChR activation. Finally, the promoting effects of SLURP1 on the pathogenesis of E. coli K1 meningitis was significantly abolished in the alpha 7 nAChR knockout mice. These results reveal that E. coli K1 exploits SLURP1 to activate alpha 7 nAChR and facilitate its pathogenesis, and blocking SLURP1-alpha 7 nAChR interaction might represent a novel therapeutic strategy for E. coli K1 meningitis.

Automated summary

E. coli K1 infection triggers the release of SLURP1, an endogenous ligand of alpha 7 nAChR, which is crucial for E. coli K1 invasion and neutrophil migration across the BBB. SLURP1 is also required for E. coli K1-induced alpha 7 nAChR activation.