Heterogeneity of macrophage activation in fish

• Published in: Developmental and comparative immunology 2011-12, Vol.35 (12), p.1246-1255
• Main Authors: Forlenza, Maria, Fink, Inge R., Raes, Geert, Wiegertjes, Geert F.
• Format: Article
• Language: English
• Subjects: Alternatively activated macrophages; Animals; Arginase; Arginase - immunology; Arginase - metabolism; Bacteria - immunology; Bacterial Infections - immunology; Bacterial Infections - microbiology; Biomarkers - metabolism; carassius-auratus l; carp; Classically activated macrophages; cyprinus-carpio l; enzyme activity; expression analysis; factor-alpha; Fish; Fish Diseases - immunology; Fish Diseases - microbiology; Fishes - genetics; Fishes - immunology; Fishes - microbiology; Free Radicals - immunology; genes; Immunity, Innate; in vitro studies; in vivo studies; iNOS; Interferon-gamma - immunology; Interferon-gamma - pharmacology; interferon-gamma genes; interleukin-10; Interleukin-10 - biosynthesis; Interleukin-10 - immunology; interleukin-13; Interleukin-13 - biosynthesis; Interleukin-13 - immunology; interleukin-4; Interleukin-4 - biosynthesis; Interleukin-4 - immunology; ligands; Lipopolysaccharides - immunology; Lipopolysaccharides - pharmacology; macrophage activation; Macrophage Activation - drug effects; Macrophage Activation - immunology; macrophages; Macrophages - cytology; Macrophages - immunology; Macrophages - metabolism; mammals; Nitric Oxide Synthase Type II - immunology; Nitric Oxide Synthase Type II - metabolism; nitric-oxide synthase; parasitoses; phagocytosis; Phagocytosis - immunology; phenotype; proteins; rainbow-trout; Species Specificity; Teleost; TLR; toll-like receptors; Toll-Like Receptors - immunology; trout oncorhynchus-mykiss; tumor-necrosis-factor
• ISSN: 0145-305X; 1879-0089
• DOI: 10.1016/j.dci.2011.03.008

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.