ACKR4a induces autophagy to block NF-κB signaling and apoptosis to facilitate Vibrio harveyi infection

Autophagy and apoptosis are two recognized mechanisms of resistance to bacterial invasion. However, bacteria have likewise evolved the ability to evade immunity. In this study, we identify ACKR4a, a member of an atypical chemokine receptor family, as a suppressor of the NF-kappa B pathway, which cooperates with Beclin-1 to induce autophagy to inhibit NF-kappa B signaling and block apoptosis, facilitating Vibrio harveyi infection. Mechanistically, V. harveyi-induced Ap-1 activates ACKR4a transcription and expression. ACKR4a forms a complex with Beclin-1 and MyD88, respectively, inducing autophagy and transporting MyD88 into the lysosome for degradation to suppress inflammatory cytokine production. Meanwhile, ACKR4a-induced autophagy blocks apoptosis by inhibiting caspase8. This study proves for the first time that V. harveyi uses both autophagy and apoptosis to evade innate immunity, suggesting that V. harveyi has evolved the ability to against fish immunity.