An Essential Role for the Hv1 Voltage-gated Proton Channel in Corneal Infection

Overview

Journal bioRxiv

Date 2024 Jul 29

PMID 39071375

Authors

Priscila Rodriguez

Serena Abbondante

Michaela Marshall

Jessica Abdelmeseh

Francesco Tombola

Eric Pearlman

Affiliations

Soon will be listed here.

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 blinding corneal infection and found that in contrast to C57BL/6 mice, mice exhibit an impaired ability to kill bacteria and regulate disease severity. , 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 with . Collectively, these findings demonstrate an important role for Hv1 on controlling bacterial growth in a clinically relevant bacterial infection model.

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