Influenza coinfection inhibits control of mycobacterial infection in a human challenge model

Influenza coinfection inhibits control of mycobacterial infection in a human challenge model | 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 Influenza coinfection inhibits control of mycobacterial infection in a human challenge model Claire Broderick, Oliver Powell, Samuel Nichols, Giselle D'Souza, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6648705/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 Mycobacterium tuberculosis infection is a dynamic continuum. Clinical outcomes reflect complex host-pathogen interactions. Epidemiological and animal studies have suggested influenza coinfection as a risk factor for progression from contained infection to active disease, but human studies have been lacking. Using a whole blood luminescent mycobacterial growth inhibition assay within a human influenza challenge study, we show that influenza infection reduces immunological control of mycobacterial growth. Transcriptome-wide RNA sequencing, cytokine and cellular analyses of subjects’ blood before and after influenza infection showed that innate immune pathways, including type 1 interferon signalling, are activated by influenza but their subsequent responsiveness to mycobacteria is reduced, with multiple genes’ responses to BCG lux infection repressed by influenza coinfection. The data suggest that influenza infection impairs immune mechanisms that contain mycobacterial growth and may be a risk factor for tuberculosis (TB) disease. Influenza vaccination might offer high risk, high prevalence populations protection against TB disease. Biological sciences/Immunology/Infectious diseases/Tuberculosis Biological sciences/Immunology/Infectious diseases/Influenza virus Health sciences/Medical research/Experimental models of disease Biological sciences/Computational biology and bioinformatics Health sciences/Diseases/Infectious diseases/Tuberculosis Tuberculosis mycobacteria BCG influenza coinfection interferon challenge model immune response Full Text Additional Declarations There is NO Competing Interest. Supplementary Files InventoryofSupportingInformation.pdf Inventory of Supporting Information Extendeddata.pdf Extended data SupplementaryTables.pdf Supplementary Tables 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. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6648705","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":457140630,"identity":"275fc882-eb2a-456b-9004-6981b5865b58","order_by":0,"name":"Claire 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