Leishmania exploits the macrophage m6A reader IGF2BP2 for glycolytic reprogramming and host cell survival

Leishmania exploits the macrophage m6A reader IGF2BP2 for glycolytic reprogramming and host cell survival | 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 Leishmania exploits the macrophage m 6 A reader IGF2BP2 for glycolytic reprogramming and host cell survival Gerald Späth, Sheng Zhang, Hervé Lecoeur, Hugo Varet, Rachel Legendre, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6881164/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 We uncover a novel, epitranscriptomic strategy evolved in Leishmania parasites to subvert macrophage function enabling long-term infection. This mechanism targets the macrophage m 6 A reader protein IGF2BP2, inducing a unique phenotype in Leishmania-infected macrophages (LIMs) integrating characteristics specifically associated with Leishmania infection with features of M1 and M2 polarization. LIMs undergo a metabolic shift from an early M2-like state relying on respiratory energy production to a late M1-like state characterized by aerobic glycolysis and lactate secretion. Unlike typical M1 macrophages, this glycolytic shift in LIMs is not associated with HIF1-α induction but relies on IGF2BP2-mediated mRNA stabilization of hexokinase 2, a key glycolytic enzyme. Knock down of IGF2BP2 expression reduces glycolytic capacity and interferes with LIMs viability, which is rescued by lactate addition. These results reveal the importance of metabolic reprogramming in chronic Leishmania infection and uncover a novel, m 6 A-dependent subversion mechanism that likely has broader implications for other macrophage-targeting pathogens. Biological sciences/Immunology/Immune evasion Health sciences/Diseases/Infectious diseases/Parasitic infection Macrophage Leishmania metabolism polarization IGF2BP2 Glycolysis Full Text Additional Declarations There is NO Competing Interest. 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-6881164","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":472539263,"identity":"3c25e39d-f064-45e0-829a-9e246281fffd","order_by":0,"name":"Gerald 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