We found that in the stage of E. coli K1-induced BBB disruptions, α7nAChR functioned as the key regulator that affects the integrity of HBMECs by activating the JAK2–STAT5 signaling pathway, while CISH inhibited JAK2–STAT5 activation and exhibited protective effects against E. coli infection. Here, CISH is linked to escherichia coli infection.