title: Phagocytosis of mycobacteria by zebrafish macrophages is dependent on the scavenger receptor Marco, a key control factor of pro-inflammatory signalling.
abstract: Scavenger receptors on the cell surface of macrophages play an important role in host defence through their ability to bind microbial ligands and induce phagocytosis. Concurrently, signal transduction pathways are initiated that aid in defence mechanisms against the invading microbe. Here we report on the function of scavenger receptor Marco (Macrophage receptor with collagenous structure) during infection of zebrafish embryos with Mycobacterium marinum, a close relative of M. tuberculosis. Morpholino knockdown demonstrates that Marco is required for the rapid phagocytosis of M. marinum following intravenous infection. Furthermore, gene expression analysis shows that Marco controls the initial transient pro-inflammatory response to M. marinum and remains a determining factor for the immune response signature at later stages of infection. Increased bacterial burden following marco knockdown indicates that this scavenger receptor is important for control of M. marinum growth, likely due to delayed phagocytosis and reduced pro-inflammatory signalling observed under conditions of Marco deficiency.
authors.affiliation: Institute of Biology, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Benard
authors.affiliation: Institute of Biology, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Roobol
authors.affiliation: Institute of Biology, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
authors.forename: Herman P
authors.initials: HP
authors.lastname: Spaink
authors.affiliation: Institute of Biology, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands. Electronic address: a.h.meijer@biology.leidenuniv.nl.
authors.forename: Annemarie H
authors.initials: AH
authors.lastname: Meijer
mesh_terms: D000818:Animals; D058491:Bacterial Load; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D060172:Morpholinos / Q000235:genetics; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D019910:Mycobacterium marinum; D010587:Phagocytosis / Q000235:genetics*; D051116:Receptors, Scavenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D015027:Zebrafish / Q000235:genetics / Q000276:immunology*
chemical_list: D060172:Morpholinos; D051116:Receptors, Scavenger
keywords: Infection; Innate immunity; Marco; Mycobacterium marinum; Phagocytosis; Scavenger receptor