Dual oxidase 1 promotes antiviral innate immunity

Area of Science:

• Immunology
• Respiratory Medicine
• Biochemistry

Background:

• Dual oxidase 1 (DUOX1), an NADPH oxidase, is expressed in respiratory cells and generates hydrogen peroxide (H2O2) in airways.
• Previous in vitro studies suggested DUOX1 and lactoperoxidase (LPO) collaborate to produce antimicrobial hypothiocyanite (OSCN-).
• The in vivo function of DUOX1 in mammalian antiviral immunity remained unproven.

Purpose of the Study:

• To investigate the in vivo role of DUOX1 in mammalian antiviral innate immunity.
• To elucidate the mechanism by which DUOX1 contributes to host defense against influenza virus.
• To explore the therapeutic potential of enhancing DUOX1-mediated antiviral mechanisms.

Main Methods:

• Utilized Duox1-deficient (Duox1-/-) mice challenged with influenza virus.
• Assessed mortality, morbidity, viral clearance, cytokine levels, immune cell recruitment, and epithelial apoptosis.
• Investigated OSCN- generation and antiviral activity using primary human tracheobronchial epithelial cells and influenza virus in vitro, employing H2O2 scavenger catalase.

Main Results:

• Duox1-/- mice exhibited increased mortality, morbidity, and impaired lung viral clearance following influenza challenge.
• DUOX1 modulated airway cytokine levels, innate immune cell recruitment, and epithelial apoptosis.
• In vitro, LPO-generated OSCN- using DUOX1-derived H2O2 inactivated influenza virus, reduced viral replication and RNA synthesis, and inhibited viral binding and entry.
• OSCN- did not affect influenza neuraminidase activity or morphology.

Conclusions:

• DUOX1 plays a critical role in promoting antiviral innate immunity in vivo.
• The DUOX1-LPO-H2O2-OSCN- axis is a key component of airway defense against influenza virus.
• Targeting and boosting this DUOX1-mediated antiviral mechanism offers potential therapeutic strategies for viral infections.