An essential role for the Hv1 voltage-gated proton channel inPseudomonas aeruginosacorneal infection

Abstract

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). In contrast, the role of the Hv1 voltage-gated proton channel that is required for sustained NOX2 activity is less well characterized. We examined the role of Hv1 in a murine model of blindingPseudomonas aeruginosacorneal infection and found that in contrast to C57BL/6 mice,Hvcn1-/-mice exhibit an impaired ability to kill bacteria and regulate disease severity.In vitro, we used a novel Hv1 Inhibitor Flexible (HIF) to block ROS production by human and murine neutrophils and found that HIF inhibits ROS production in a dose-dependent manner following stimulation with PMA or infection withP. aeruginosa. Collectively, these findings demonstrate an important role for Hv1 on controlling bacterial growth in a clinically relevant bacterial infection model.