title: Teleost soluble CSF-1R modulates cytokine profiles at an inflammatory site, and inhibits neutrophil chemotaxis, phagocytosis, and bacterial killing.
abstract: Soluble colony stimulating factor-1 receptor (sCSF-1R) is a novel bony fish protein that contributes to the regulation of macrophage proliferation. We recently showed that this soluble receptor is highly upregulated by teleost macrophages in the presence of apoptotic cells. Further, recombinant sCSF-1R inhibited leukocyte infiltration into a challenge site in vivo. Herein, we characterized the mechanisms underlying these changes as a platform to better understand the evolutionary origins of the CSF-1 immune-regulatory axis and inflammation control in teleosts. Using an in vivo model of self-resolving peritonitis, we show that sCSF-1R downregulates chemokine expression and inhibits neutrophil chemotaxis. Soluble CSF-1R also inhibited gene expression of several pro-inflammatory cytokines and promoted the expression of an anti-inflammatory mediator, IL-10. Finally, the phenotype of infiltrating neutrophils changed significantly in the presence of sCSF-1R. Both a reduced capacity for phagocytosis and pathogen killing were observed. Overall, our results implicate sCSF-1R as an important regulator of neutrophil responses in teleosts. It remains unclear whether this represents an inflammation regulatory factor that is unique to this animal group or one that may be evolutionarily conserved and continues to contribute to the regulation of antimicrobial processes at inflammatory sites in higher vertebrates.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2P5, Canada.
authors.forename: Aja M
authors.initials: AM
authors.lastname: Rieger
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2P5, Canada.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Havixbeck
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2P5, Canada; School of Public Health, University of Alberta, Edmonton, Alberta T6G 2P5, Canada.
authors.forename: Miodrag
authors.initials: M
authors.lastname: Belosevic
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2P5, Canada; Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta T6G 2P5, Canada. Electronic address: dan.barreda@ualberta.ca.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Barreda
mesh_terms: D000333:Aeromonas / Q000276:immunology; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002464:Cell Migration Inhibition / Q000276:immunology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D029941:Fish Proteins / Q000276:immunology; D006054:Goldfish / Q000276:immunology*; D056747:Immunomodulation / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D010538:Peritonitis / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
chemical_list: D016207:Cytokines; D029941:Fish Proteins; D011994:Recombinant Proteins; D016753:Interleukin-10; D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: CSF-1; Inflammation; Neutrophil; Phagocytosis; Soluble CSF-1R