An essential role for the Hv1 voltage-gated proton channel in Pseudomonas aeruginosa corneal infections

Assembly of NADPH oxidase 2 (NOX2) proteins in neutrophils plays an essential role in controlling microbial infections by producing high levels of reactive oxygen species (ROS). We reported that neutrophils and NOX2 are required to control P. aeruginosa in a clinically relevant murine model of blinding corneal infection. Given the published role for the voltage-gated proton channel Hv1 in sustaining NOX2-mediated ROS production, we examined the role of Hv1 in P. aeruginosa keratitis. Hvcn1-/- mice exhibited an impaired ability to kill bacteria that was associated with reduced neutrophil recruitment to infected corneas. Unlike earlier reports, we found that Hvcn1-/- neutrophils produce more rather than less ROS compared with control neutrophils infected with P. aeruginosa or stimulated with PMA or zymosan. Collectively, we demonstrate that Hv1 has an important role in control of bacterial growth by neutrophils in bacterial infection beyond the regulation of ROS production.