In vivo regulation of infected and bystander monocyte phenotype by the Mycobacterium marinum ESX-1 type VII secretion system

In vivo regulation of infected and bystander monocyte phenotype by the Mycobacterium marinum ESX-1 type VII secretion system | 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 In vivo regulation of infected and bystander monocyte phenotype by the Mycobacterium marinum ESX-1 type VII secretion system Kristina Munke, Line Wulff, Julia Lienard, Fredric Carlsson, William Agace This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4999318/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Feb, 2025 Read the published version in Scientific Reports → Version 1 posted 12 You are reading this latest preprint version Abstract Pathogenic mycobacteria require the conserved ESX-1 type VII secretion system to cause disease. Using a murine Mycobacterium marinum infection model we recently demonstrated an antagonistic interplay between neutrophils and monocytes, where monocytes play a host-protective role by restricting ESX-1-dependent intragranuloma accumulation of neutrophils. Here, we demonstrate that the protective function of monocytes is maintained in RAG-deficient mice, indicating that their ability to restrict neutrophil-dependent inflammation is independent of adaptive immunity. Further, we performed single cell RNA sequencing of infected and bystander Ly6C+MHCII+ monocytes, isolated from the infected tissue, to explore how M. marinum and ESX-1 alter the monocyte phenotype in vivo. Our findings indicate that M. marinum intrinsically impacts on the transcription profile of infected monocytes in an ESX-1-independent fashion. Infection alters cytokine expression, induces glycolytic metabolism, hypoxia-mediated signaling, nitric oxide synthesis, tissue remodeling, and suppresses responsiveness to IFNg. In contrast to infected cells, the phenotype of bystander monocytes is extrinsically regulated in an ESX-1-dependent manner, including a reduced responsiveness to IFNg. These findings suggest that mycobacterial infection has pleiotropic effects on monocyte phenotype, with potential implications in bacterial growth restriction and granuloma formation. Biological sciences/Immunology Biological sciences/Microbiology Full Text Additional Declarations No competing interests reported. Supplementary Files TableS1.TotalDEGsforinfectedversusbystandercells..xlsx TableS2.TotalDEGsforWTEspKversusRD1infectedcells..xlsx TableS3.TotalDEGsforWTversusRD1bystandercells..xlsx SupplementartyinformationMunkeetal2024.docx Cite Share Download PDF Status: Published Journal Publication published 07 Feb, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 30 Sep, 2024 Reviews received at journal 30 Sep, 2024 Reviews received at journal 23 Sep, 2024 Reviews received at journal 15 Sep, 2024 Reviewers agreed at journal 15 Sep, 2024 Reviewers agreed at journal 11 Sep, 2024 Reviewers agreed at journal 11 Sep, 2024 Reviewers invited by journal 11 Sep, 2024 Editor assigned by journal 10 Sep, 2024 Editor invited by journal 10 Sep, 2024 Submission checks completed at journal 09 Sep, 2024 First submitted to journal 29 Aug, 2024 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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