title: An inducible transgene reports activation of macrophages in live zebrafish larvae.
abstract: Macrophages are the most functionally heterogenous cells of the hematopoietic system. Given many diseases are underpinned by inappropriate macrophage activation, macrophages have emerged as a therapeutic target to treat disease. A thorough understanding of what controls macrophage activation will likely reveal new pathways that can be manipulated for therapeutic benefit. Live imaging fluorescent macrophages within transgenic zebrafish larvae has provided a valuable window to investigate macrophage behavior in vivo. Here we describe the first transgenic zebrafish line that reports macrophage activation, as evidenced by induced expression of an immunoresponsive gene 1(irg1):EGFP transgene. When combined with existing reporter lines that constitutively mark macrophages, we reveal this unique transgenic line can be used to live image macrophage activation in response to the bacterial endotoxin lipopolysaccharide and xenografted human cancer cells. We anticipate the Tg(irg1:EGFP) line will provide a valuable tool to explore macrophage activation and plasticity in the context of different disease models.
authors.affiliation: Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
authors.forename: Leslie E
authors.initials: LE
authors.lastname: Sanderson
authors.affiliation: Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
authors.forename: An-Tzu
authors.initials: AT
authors.lastname: Chien
authors.affiliation: Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Astin
authors.affiliation: Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Crosier
authors.affiliation: Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Crosier
authors.affiliation: Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand. Electronic address: c.hall@auckland.ac.nz.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hall
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001943:Breast Neoplasms / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics; D007814:Larva / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic / Q000235:genetics; D014183:Transplantation, Heterologous; D015027:Zebrafish / Q000235:genetics* / Q000276:immunology; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D029961:Zebrafish Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D006836:Hydro-Lyases; C569511:Irg1L protein, zebrafish
keywords: Cancer; Immunity; Infection; Macrophage; Transgenic; Zebrafish