title: Divergent antiviral roles of amphibian (Xenopus laevis) macrophages elicited by colony-stimulating factor-1 and interleukin-34.
abstract: Macrophages are integral to amphibian immunity against RVs, as well as to the infection strategies of these pathogens. Although CSF-1 was considered to be the principal mediator of macrophage development, the IL-34 cytokine, which shares no sequence identity with CSF-1, is now believed to contribute to vertebrate monopoiesis. However, the respective roles of CSF-1- and IL-34-derived macrophages are still poorly understood. To delineate the contribution of these macrophage populations to amphibian immunity against the RV FV3, we identified the Xenopus laevis IL-34 and transcriptionally and functionally compared this cytokine with the previously identified X. laevis CSF-1. The X. laevis CSF-1 and IL-34 displayed strikingly nonoverlapping developmental and tissue-specific gene-expression patterns. Furthermore, only CSF-1 but not IL-34 was up-regulated in the kidneys of FV3-challenged tadpoles. Intriguingly, recombinant forms of these cytokines (rXlCSF-1, rXlIL-34) elicited morphologically distinct tadpole macrophages, and whereas rXlCSF-1 pretreatment decreased the survival of FV3-infected tadpoles, rXlIL-34 administration significantly prolonged FV3-challenged animal survival. Compared with rXlIL-34-elicited macrophages, macrophages derived by rXlCSF-1 were more phagocytic but also significantly more susceptible to in vitro FV3 infections. By contrast, rXlIL-34-derived macrophages exhibited significantly greater in vitro antiranaviral activity and displayed substantially more robust gene expression of the NADPH oxidase components (p67(phox), gp91(phox)) and type I IFN. Moreover, FV3-challenged, rXlIL-34-derived macrophages exhibited several orders of magnitude greater up-regulation of the type I IFN gene expression. This marks the first report of the disparate roles of CSF-1 and IL-34 in vertebrate antiviral immunity.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Leon
authors.initials: L
authors.lastname: Grayfer
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA jacques_robert@urmc.rochester.edu.
authors.forename: Jacques
authors.initials: J
authors.lastname: Robert
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000254:growth & development / Q000378:metabolism; D002478:Cells, Cultured; D002633:Chemotaxis; D004266:DNA Virus Infections / Q000276:immunology / Q000821:virology; D060467:Disease Resistance; D018507:Gene Expression Regulation, Developmental; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D007814:Larva; D008099:Liver / Q000254:growth & development / Q000378:metabolism; D008168:Lung / Q000254:growth & development / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis; D010802:Phylogeny; D017995:Ranavirus / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000254:growth & development / Q000378:metabolism; D014982:Xenopus laevis / Q000254:growth & development / Q000276:immunology* / Q000821:virology
chemical_list: D007378:Interleukins; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor
keywords: CSF-1; FV3; IL-34; immunity; ranavirus