title: Heterogeneity of macrophage activation in fish.
abstract: In this review, we focus on four different activation states of fish macrophages. In vitro, stimulation with microbial ligands induces the development of innate activated macrophages whereas classically activated macrophages can be induced by stimulation with LPS in combination with (recombinant) IFNγ. Both types of macrophages show elevated phagocytic activity, expression of pro-inflammatory cytokine genes and radical production. Alternatively activated macrophages require the cytokines IL-4/IL-13 for induction of, among others, arginase activity. Until in vitro studies identify the effects of putative IL-4 and IL-13 homologues on fish macrophages, arginase enzyme activity remains the most reliable marker for the presence of alternatively activated macrophages in fish. The best evidence for the existence of regulatory macrophages, associated with the presence of IL-10, comes from in vivo studies, for example during parasitic infections of carp. Altogether, differentially activated macrophages in fish largely resemble the phenotypes of mammalian macrophages. However, the presence of fish-specific ligand recognition by TLRs and of duplicated genes coding for proteins with particular activities, poses additional challenges for the characterization of phenotype-specific gene signatures and cell surface markers.
authors.affiliation: Department of Animal Sciences, Cell Biology and Immunology Group, Wageningen Institute of Animal Sciences, Wageningen University, P.O. Box 338, 6700 AH, Wageningen, The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Forlenza
authors.forename: Inge R
authors.initials: IR
authors.lastname: Fink
authors.forename: Geert
authors.initials: G
authors.lastname: Raes
authors.forename: Geert F
authors.initials: GF
authors.lastname: Wiegertjes
mesh_terms: D000818:Animals; D001119:Arginase / Q000276:immunology / Q000378:metabolism; D001419:Bacteria / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D015415:Biomarkers / Q000378:metabolism; D005393:Fish Diseases / Q000276:immunology* / Q000382:microbiology; D005399:Fishes / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D005609:Free Radicals / Q000276:immunology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D013045:Species Specificity; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D015415:Biomarkers; D005609:Free Radicals; D018793:Interleukin-13; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D001119:Arginase