Human Alveolar Macrophage Function is Impaired in Tuberculosis Contacts With Diabetes

Human Alveolar Macrophage Function is Impaired in Tuberculosis Contacts With Diabetes | 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 Human Alveolar Macrophage Function is Impaired in Tuberculosis Contacts With Diabetes Katharina Ronacher, Léanie Kleynhans, Carine Kunsevi-Kilola, Happy Tshivhula, and 16 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5489046/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Nov, 2025 Read the published version in EBioMedicine → Version 1 posted You are reading this latest preprint version Abstract Type 2 diabetes (T2D) increases susceptibility to tuberculosis (TB) with the underlying mechanisms remaining unknown. To determine whether immune dysfunction in the lung contributes to TB susceptibility, we obtained paired human alveolar macrophages (HAMs) and monocyte-derived macrophages (MDMs) from TB-exposed individuals with/without T2D. Upon infection with Mycobacterium tuberculosis (M.tb), T2D-HAMs had more M.tb growth and produced more TNF. There were fewer neutrophils in the bronchoalveolar lavage of T2D patients which was inversely correlated with M.tb growth. Both T2D-HAMs and MDMs expressed less CD32, with T2D patients having fewer M1-like MDMs. T2D-MDMs produced less IL-1RA and CSF2. Overall M.tb-induced gene expression was delayed in T2D-HAMs, but genes involved in negative regulation of neutrophil migration were upregulated. T2D-HAM DNA was hypermethylated compared to control HAMs, however genes linked to TNF signalling were hypomethylated. We show here the first in-depth analysis of T2D-HAMs providing an explanation for more severe TB in T2D patients. Biological sciences/Immunology/Infectious diseases/Tuberculosis Biological sciences/Immunology/Innate immune cells/Monocytes and macrophages/Alveolar macrophages tuberculosis type 2 diabetes mycobacterial growth alveolar macrophages monocyte derived macrophages bronchoalveolar lavage Full Text Additional Declarations There is NO Competing Interest. Supplementary Files KleynhansSupplementalMaterial.pdf Supplemental material, figures and tables Cite Share Download PDF Status: Published Journal Publication published 30 Nov, 2025 Read the published version in EBioMedicine → 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. 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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-5489046","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":381347852,"identity":"0016980f-dbbf-47a7-9506-d17e63c640d2","order_by":0,"name":"Katharina 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