PUBLICATION

The DC-SIGN of Zebrafish: Insights into the Existence of a CD209 Homologue in a Lower Vertebrate and Its Involvement in Adaptive Immunity

Authors
Lin, A.F., Xiang, L.X., Wang, Q.L., Dong, W.R., Gong, Y.F., and Shao, J.Z.
ID
ZDB-PUB-091120-20
Date
2009
Source
Journal of immunology (Baltimore, Md. : 1950)   183(11): 7398-7410 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Adaptive Immunity*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Adhesion Molecules/genetics*
  • Cell Adhesion Molecules/immunology*
  • Cell Adhesion Molecules/metabolism*
  • Cloning, Molecular
  • Conserved Sequence
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Lectins, C-Type/genetics*
  • Lectins, C-Type/immunology*
  • Lectins, C-Type/metabolism*
  • Male
  • Molecular Sequence Data
  • Phylogeny
  • Receptors, Cell Surface/genetics*
  • Receptors, Cell Surface/immunology*
  • Receptors, Cell Surface/metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Zebrafish/immunology*
PubMed
19890038 Full text @ J. Immunol.
Abstract
Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN/CD209) has become hot topic in recent studies because of its important roles in immune responses and immune escape. CD209 has been well characterized in humans and several other mammals, but little documentation exists about it in lower vertebrates. This is the first report on the identification and functional characterization of a fish DC-SIGN/CD209 molecule. The zebrafish DC-SIGN/CD209 cDNA translates into 343 aa organized into three domains structurally conserved among vertebrates. An EPN motif essential for interacting with Ca(2+) and for recognizing mannose-containing motifs has been identified. Several conserved motifs crucial for internalization and signal transduction are also present within the cytoplasmic tail. Phylogenetic analysis supports the hypothesis that CD209 family members diverged from a common ancestor. The expression of DC-SIGN/CD209 in immune-related tissues can be significantly up-regulated by exogenous Ags and IL-4. This molecule associates with various APCs, including macrophages, B lymphocytes, and a possible dendritic cell-like (CD83(+)/CD80(+)CD209(+)) population. Functionally, T cell activation, Ab (IgM) production, and bacterial vaccination-elicited immunoprotection can be dramatically inhibited by a CD209 blockade after stimulation with keyhole limpet hemocyanin (KLH) in vivo or challenged with Aeromonas hydrophila, suggesting that DC-SIGN/CD209 in zebrafish is crucial for the initiation and development of adaptive immunity. Phagocytosis analysis showed that DC-SIGN/CD209 does not participate in the uptake of KLH Ag, suggesting that other mechanisms might exist that underlie DC-SIGN/CD209 involvement. We hope that the present study will contribute to a better cross-species understanding of the evolutionary history of the DC-SIGN/CD209 family.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping