Protective coinfection: influenza reprograms myeloid cells to limit CD8 T cell–mediated malaria pathology

Protective coinfection: influenza reprograms myeloid cells to limit CD8 T cell–mediated malaria pathology | 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 Protective coinfection: influenza reprograms myeloid cells to limit CD8 T cell–mediated malaria pathology Tracey Lamb, Jenna Reed, Ritika Nayan, Margot Deckers, Douglas Cornwall, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9404453/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 Malaria-associated acute lung injury (MA-ALI) is a life-threatening complication of malaria driven by pathogenic CD8 T cell responses with no effective pharmaceutical interventions. Here, we show that co-infection with non-lethal influenza/A/HKx31 (X31) protects mice from malarial pulmonary vascular leak and death. X31 co-infection drove the expansion of Ly6C+ monocyte-derived alveolar macrophages, which inhibited pathogenic CD8 T cells in a contact-dependent manner. Moreover, in vivo blockade of monocytic myeloid cells with gemcitabine eliminated the protective phenotype. Protection occurred independently of parasite burden and did not require type I interferon signaling. Instead, co-infected pulmonary CD8 T cells exhibited broad transcriptional reprogramming and impaired inflammatory cytokine production. Our findings demonstrate that virus-induced myeloid cells suppress pulmonary CD8 T cells to prevent lung immunopathology in severe malaria. This work suggests that therapeutics that expand suppressive myeloid cells should be considered for adjunctive therapy for MA-ALI. Health sciences/Pathogenesis/Infection Biological sciences/Immunology/Infectious diseases/Parasitic infection Biological sciences/Immunology/Innate immune cells/Monocytes and macrophages/Alveolar macrophages Biological sciences/Immunology/Infectious diseases/Influenza virus Biological sciences/Immunology/Inflammation/Acute inflammation Plasmodium lung injury influenza myeloid cells immune suppression CD8 T cells Malaria malaria-associated acute lung injury co-infection arginase Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementalFigures.xlsx Supplemental Figures Data 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. 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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-9404453","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":636366541,"identity":"f322bb2c-ad1f-422f-8e8f-2779d8bea3b9","order_by":0,"name":"Tracey 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