Interaction between TREM2-Macrophages and Cutibacterium acnes Drives Altered Lipid Metabolism in Chronic Apical Periodontitis

Interaction between TREM2-Macrophages and Cutibacterium acnes Drives Altered Lipid Metabolism in Chronic Apical Periodontitis | 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 Interaction between TREM2-Macrophages and Cutibacterium acnes Drives Altered Lipid Metabolism in Chronic Apical Periodontitis Jong In YOOK, Dawool Han, Nam Hee Kim, Seung-Yong Han, Hyeeun Song, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9466880/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 Chronic periapical periodontitis (CAP), highly prevalent worldwide, has long been regarded as non-specific inflammation. Lipophilic Cutibacerium acnes (CA) persistence in host macrophages has emerged as the pathologic background of sarcoidosis and acne vulgaris. Here we report that intracellular persistence of CA in TREM2-macrophages plays a pathologic role in CAP. We observed persistent CA in macrophages in most CAP samples. Our CA clinical isolates persist in the cytosolic space of macrophages, retarding phagolysosomal degradation accompanied by NLRP3-dependent inflammatory response. Subcutaneous injection of those isolates in vivo recapitulates subcutaneous aggregation of CA-laden macrophages. By single cell RNA sequencing analysis of defined CAP samples, we found that CA in TREM2-macrophages drives exuberant lipid droplets formation, indicating that immune cells are potential lipid provider in CAP. Our observations elucidate the mechanistic link whereby TREM2-macrophages and altered lipid metabolism provide a lipid-rich niche for CA, contributing to the pathophysiology of CAP. Health sciences/Pathogenesis/Inflammation/Chronic inflammation Biological sciences/Cell biology/Mechanisms of disease Cutibacterium acnes Chronic apical periodontitis TREM2 macrophage Lipid metabolism Sarcoidosis Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SuppleTab13.Demographicandclinicalinformation.docx Demograthic and clinical information Raw264.7.wmv Phagocytic activity of RAW264.7 cells THP1.wmv Phagocytic activity of THP-1 cells PBMCs.wmv Phagocytic activity of PBMC-derived macrophages ExtendedDataFigures.pptx Extended Data Figure 1-10 SuppleTab4lipidgenesets.xlsx Lipid gene list for single cell RNA analysis 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-9466880","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":630395303,"identity":"4d46d81d-558c-448d-8443-4cf37ce160fe","order_by":0,"name":"Jong In 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