Neutrophil NADPH oxidase breaks the inflammatory IL-1β/IL-17A circuit to enhance pathogen clearance during respiratory virus infections.

Neutrophil NADPH oxidase breaks the inflammatory IL-1β/IL-17A circuit to enhance pathogen clearance during respiratory virus infections. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Neutrophil NADPH oxidase breaks the inflammatory IL-1β/IL-17A circuit to enhance pathogen clearance during respiratory virus infections. Annika Warnatsch, Aderonke Sofoluwe, Angelos Petropoulos, Abhilesh Goomanee, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5145371/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Respiratory virus infections are invariably accompanied by an increase in oxidative stress, characterised by elevated production of Reactive Oxygen Species (ROS) in the lung, which plays a pivotal role in both pathogenesis and host defence. Using a mouse model, neutrophil NADPH Oxidase 2 (Nox2) emerges as a key player, primarily responsible for generation of ROS during the early phases of Influenza A Virus (IAV) infection. Neutrophil Nox2-derived ROS display a multifaceted role, not only unleashing oxidative stress but in turn curbing neutrophil-derived IL-1β signalling. Absence of neutrophil Nox2 triggered heightened production of IL-1β, promoting the proliferation of IL-17-producing gamma delta (γδ) T cells. This early self-amplified augmentation of the IL-1β/IL-17 axis counteracted the antiviral interferon response against IAV infection in mice. We extended our findings to humans. Similar patterns of ROS production and cytokine regulation were observed in human neutrophils when exposed to virus analogue poly(I:C) and SARS-CoV-2. Our discovery highlights that ROS, often associated with harm, play a dual role by regulating cytokine signalling and thus influencing the immune response against respiratory viruses. Biological sciences/Immunology/Innate immune cells/Granulocytes/Neutrophils Biological sciences/Immunology/Infection Biological sciences/Immunology/Inflammation/Acute inflammation Biological sciences/Immunology/Cytokines/Interleukins Full Text Additional Declarations There is NO Competing Interest. Supplementary Files AWarnatschMaterialsandMethods.pdf AWarnatschSupplementalinformation.pdf NCOMMS2461358nrreportingsummaryAW.pdf Article File - reporting summary Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Using a mouse model, neutrophil NADPH Oxidase 2 (Nox2) emerges as a key player, primarily responsible for generation of ROS during the early phases of Influenza A Virus (IAV) infection. Neutrophil Nox2-derived ROS display a multifaceted role, not only unleashing oxidative stress but in turn curbing neutrophil-derived IL-1β signalling. Absence of neutrophil Nox2 triggered heightened production of IL-1β, promoting the proliferation of IL-17-producing gamma delta (γδ) T cells. This early self-amplified augmentation of the IL-1β/IL-17 axis counteracted the antiviral interferon response against IAV infection in mice. We extended our findings to humans. Similar patterns of ROS production and cytokine regulation were observed in human neutrophils when exposed to virus analogue poly(I:C) and SARS-CoV-2. 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