Blood Journal
Leading the way in experimental and clinical research in hematology

Characterization of the mononuclear phagocyte system in zebrafish

  1. Valerie Wittamer1,2,*,
  2. Julien Y. Bertrand1,*,
  3. Patrick W. Gutschow1, and
  4. David Traver1,3
  1. 1Division of Biological Sciences, University of California San Diego, La Jolla, CA;
  2. 2Interdisciplinary Research Institute (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium; and
  3. 3Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA

Abstract

The evolutionarily conserved immune system of the zebrafish (Danio rerio), in combination with its genetic tractability, position it as an excellent model system in which to elucidate the origin and function of vertebrate immune cells. We recently reported the existence of antigen-presenting mononuclear phagocytes in zebrafish, namely macrophages and dendritic cells (DCs), but have been impaired in further characterizing the biology of these cells by the lack of a specific transgenic reporter line. Using regulatory elements of a class II major histocompatibility gene, we generated a zebrafish reporter line expressing green fluorescent protein (GFP) in all APCs, macrophages, DCs, and B lymphocytes. Examination of mhc2dab:GFP; cd45:DsRed double-transgenic animals demonstrated that kidney mhc2dab:GFPhi; cd45:DsRedhi cells were exclusively mature monocytes/macrophages and DCs, as revealed by morphologic and molecular analyses. Mononuclear phagocytes were found in all hematolymphoid organs, but were most abundant in the intestine and spleen, where they up-regulate the expression of inflammatory cytokines upon bacterial challenge. Finally, mhc2dab:GFP and cd45:DsRed transgenes mark mutually exclusive cell subsets in the lymphoid fraction, enabling the delineation of the major hematopoietic lineages in the adult zebrafish. These findings suggest that mhc2dab:GFP and cd45:DsRed transgenic lines will be instrumental in elucidating the immune response in the zebrafish.

  • Submitted November 26, 2010.
  • Accepted February 25, 2011.
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