Lifelong malaria exposure drives B cell activation and post-transcriptional regulation while suppressing inflammatory transcriptional programs

Lifelong malaria exposure drives B cell activation and post-transcriptional regulation while suppressing inflammatory transcriptional programs | 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 Lifelong malaria exposure drives B cell activation and post-transcriptional regulation while suppressing inflammatory transcriptional programs John Kimotho, Kioko Mwikali, Evans Mudibo, Michelle Muthui, Linda Murungi, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6974016/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Lifelong pathogen exposure can drive persistent immune remodelling, impacting responses to infections and vaccines. Malaria, with varying transmission intensity across Africa, offers a natural model to study these adaptations. We profiled peripheral blood mononuclear cells (PBMCs) and plasma soluble mediators in 60 healthy Kenyan individuals living in regions with differing malaria exposure. High-exposure individuals had 658 differentially expressed genes in PBMCs, enriched for pathways linked to B cell activity, immune regulation, and RNA processing, suggesting sustained immune activation, compensatory tolerance, and post-transcriptional control. In contrast, genes involved in inflammation and vascular responses were downregulated, consistent with immunosuppression. Plasma markers showed low-grade inflammation, pointing to a compartmentalised immune response potentially localised to tissues or specific immune-cell types. Here, we show that lifelong malaria exposure reshapes the immune system through a balance of activation and suppression, highlighting the importance of considering exposure-driven immune states when designing vaccines and immunotherapies for pathogen-endemic regions. Biological sciences/Immunology/Infectious diseases/Malaria Biological sciences/Immunology/Translational immunology Chronic exposure pathogen exposure Immune activation Immune tolerance Immunomodulation Immune imprinting Malaria. Full Text Additional Declarations Ethics Approval Statement Ethical approval was obtained from the Scientific & Ethical Review Unit (SERU), Kenya Medical Research Institute (KEMRI/SERU/4177). There is NO Competing Interest. Supplementary Files SupplementaryData.xlsx Supplementary Data SupplementaryMaterial.pdf Supplementary_Material Cite Share Download PDF Status: Posted 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-6974016","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":480781874,"identity":"9650807e-ee51-47aa-9dab-96137fdc82cc","order_by":0,"name":"John 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