Identification of dendritic antigen-presenting cells in the zebrafish

In mammals, dendritic cells (DCs) form the key link between the innate and adaptive immune systems. DCs act as immune sentries in various tissues and, upon encountering pathogen, engulf and traffic foreign antigen to secondary lymphoid tissues, stimulating antigen-specific T lymphocytes. Although DC...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-09, Vol.107 (36), p.15850-15855
Main Authors: Lugo-Villarino, Geanncarlo, Balla, Keir M., Stachura, David L., Bañuelos, Karina, Werneck, Miriam B. F., Traver, David, Glimcher, Laurie H.
Format: Article
Language:English
Subjects:
Animals
Antigen-Presenting Cells - immunology
Antigens
Arachis hypogaea
Base Sequence
Biological Sciences
Cell lines
Cells
Danio rerio
Dendritic cells
Dendritic Cells - immunology
DNA Primers
Freshwater
Immune system
Immunology
Leukocytes
Life Sciences
Lymphocytes
Mammals
Mast cells
Monocytes
Neutrophils
Pathogens
Phagocytes
Polymerase Chain Reaction
T lymphocytes
Teleostei
Zebrafish
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Summary:In mammals, dendritic cells (DCs) form the key link between the innate and adaptive immune systems. DCs act as immune sentries in various tissues and, upon encountering pathogen, engulf and traffic foreign antigen to secondary lymphoid tissues, stimulating antigen-specific T lymphocytes. Although DCs are of fundamental importance in orchestrating the mammalian immune response, their presence and function in nonmammalian vertebrates is largely unknown. Because teleosts possess one of the earliest recognizable adaptive immune systems, we sought to identify antigen-presenting cells (APCs) in the zebrafish to better understand the potential origins of DCs and their evolutionary relationship to lymphocytes. Here we present the identification and characterization of a zebrafish APC subset strongly resembling mammalian DCs. Rare DCs are present in various adult tissues, and can be enriched by their affinity for the lectin peanut agglutinin (PNA). We show that PNA hi myeloid cells possess the classical morphological features of mammalian DCs as revealed by histochemical and ultrastructural analyses, phagocytose-labeled bacterial preparations in vivo, and exhibit expression of genes associated with DC function and antigen presentation, including il12, MHC class II invariant chain iclp1, and csf1r. Importantly, we show that PNA hi cells can activate T lymphocytes in an antigen-dependent manner. Together, these studies suggest that the cellular constituents responsible for antigen presentation are remarkably conserved from teleosts to mammals, and indicate that the zebrafish may serve as a unique model to study the origin of APC subsets and their evolutionary role as the link between the innate and adaptive immune systems.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1000494107