Phagocytosis of mycobacteria by zebrafish macrophages is dependent on the scavenger receptor Marco, a key control factor of pro-inflammatory signalling

Dev Comp Immunol. 2014 Dec;47(2):223-33. doi: 10.1016/j.dci.2014.07.022. Epub 2014 Jul 30.

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.

Keywords: Infection; Innate immunity; Marco; Mycobacterium marinum; Phagocytosis; Scavenger receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Load
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Immunity, Innate
  • Macrophages / immunology*
  • Macrophages / microbiology
  • Morpholinos / genetics
  • Mycobacterium Infections, Nontuberculous / immunology
  • Mycobacterium Infections, Nontuberculous / microbiology
  • Mycobacterium Infections, Nontuberculous / veterinary*
  • Mycobacterium marinum
  • Phagocytosis / genetics*
  • Receptors, Scavenger / antagonists & inhibitors
  • Receptors, Scavenger / genetics
  • Receptors, Scavenger / immunology*
  • Signal Transduction
  • Zebrafish / genetics
  • Zebrafish / immunology*

Substances

  • Morpholinos
  • Receptors, Scavenger