Stabilin-1 mediates beneficial monocyte recruitment and tolerogenic macrophage programming during CVB3-induced viral myocarditis. (April 2022)

• Record Type: Journal Article
• Authors: Carai, Paolo; Papageorgiou, Anna Pia; Van Linthout, Sophie; Deckx, Sophie; Velthuis, Sebastiaan; Lutgens, Esther; Wijnands, Erwin; Tschöpe, Carsten; Schmuttermaier, Christina; Kzhyshkowska, Julia; Jones, Elizabeth Anne Vincent; Heymans, Stephane
• Is Part Of: Journal of molecular and cellular cardiology. Volume 165(2022)
• Page Start: 31
• Page End: 39
• Publication Date: 2022-04
• Subjects: Viral myocarditis -- Stabilin-1 -- Inflammation -- Monocytes -- Fibronectin; ARG1 Arginase 1 -- CCID50 Cell culture 50% infective dose -- CHIL3 Chitinase-like 3 -- CLEVER-1 Common Lymphatic Endothelial and Vascular Endothelial Receptor-1 -- CVB3 Coxsackievirus B3 -- DAB 3, 3′-Diaminobenzidine -- DAPI 4′, 6-Diamidino-2-phenylindole dihydrochloride -- DPI Days post-infection -- EMB Endomyocardial biopsy -- ECM Extracellular matrix -- EDA Type III repeats Extra Domain A -- EGF Epidermal growth factor -- FACS Fluorescence-activated cell sorting -- FAS1 Fasciclin 1 -- FEEL-1 Fasciclin, EGF-like, laminin-type EGF-like, and link domain-containing scavenger receptor 1 -- FN1 Fibronectin 1 -- GTS Glutathione-S-transferase -- HRP Horseradish peroxidase -- IL10 Interleukin 10 -- Ly6C Lymphocyte antigen 6 complex locus C1 -- Ly6G Lymphocyte antigen 6 complex locus G6D -- MI Myocardial infarction -- NOS2 Nitric oxide synthase 2 -- RT-PCR Real-time polymerase chain reaction -- SR-BI Scavenger receptor BI -- Treg Regulatory T lymphocyte -- TNFα Tumor necrosis factor α -- VM Viral myocarditis; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2021.12.009
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: Pathological innate and adaptive immune response upon viral infection may lead to cardiac injury and dysfunction. Stabilin-1 is a scavenger receptor that regulates several aspects of the innate immunity. Whether stabilin-1 affects the inflammatory response during viral myocarditis (VM) is entirely unknown. Here, we assess the role of stabilin-1 in the pathogenesis of VM and its suitability as a therapeutic target. Genetic loss of stabilin-1 increased mortality and cardiac necrosis in a mouse model of human Coxsackievirus B3 (CVB3)-induced myocarditis. Absence of stabilin-1 significantly reduced monocyte recruitment and strongly reduced the number of alternatively activated anti-inflammatory macrophages in the heart, enhancing a pro-inflammatory cardiac niche with a detrimental T lymphocyte response during VM. Yeast two-hybrid screening, confirmed by affinity chromatography, identified fibronectin as a stabilin-1 interacting partner. Absence of stabilin-1 specifically decreased monocyte adhesion on extracellular fibronectin in vitro. Loss of Type III repeats Extra Domain A (EDA) of fibronectin during VM also increased the mortality and cardiac necrosis as in stabilin-1 knockout mice, with reduced monocytic cardiac recruitment and increased T lymphocyte response. Collectively, stabilin-1 has an immune-suppressive role of limiting myocardial damage during VM, regulating anti-inflammatory monocyte-recruitment to the site of inflammation. Graphical abstract: Unlabelled Image Highlights: Stabilin-1 is expressed in myeloid cells in mouse and human viral myocarditis. Loss of stabilin-1 increased mortality and cardiac necrosis in murine viral myocarditis. Stabilin-1 is required for anti-inflammatory macrophage phenotype differentiation. Stabilin-1 influences monocyte recruitment through binding with extracellular fibronectin.