Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/8956
Mouse DC-SIGN/CD209a as Target for Antigen Delivery and Adaptive Immunity
Front Immunol. 2018 May 7;9:990.
The efficacy of vaccination studies aimed at targeting antigens to human DC-SIGN (hDC-SIGN) have been notoriously difficult to study in vivo, as eight dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) homologs have been described in mice. CD209a/SIGNR5 has been coined as the mouse DC-SIGN (mDC-SIGN) ortholog, based on its expression and location in the genome. Nonetheless, which properties of hDC-SIGN are covered by mDC-SIGN is poorly investigated. One of the most important functions of DC-SIGN is the induction of adaptive immunity. As such, the aim of this study is to determine the capability of mDC-SIGN to induce adaptive immune responses. Here, we show that mDC-SIGN is expressed on GM-CSF cultured bone marrow-derived dendritic cells (BMDCs) and macrophages. However, mDC-SIGN is an internalizing receptor which, unlike hDC-SIGN, quickly resurfaces after internalization. Binding of OVA-coupled anti-mDC-SIGN antibody by BMDCs leads to quick internalization, processing, and presentation to antigen-specific CD8+ and CD4+ T cells, which can be boosted using the TLR4 ligand, monophosphoryl lipid A. In the homeostatic condition, mDC-SIGN is mostly expressed on myeloid cells in the skin and spleen. A subcutaneous injection of fluorescent anti-mDC-SIGN reveals specific targeting to mDC-SIGN+ skin dendritic cells (DCs) and monocyte-derived DCs in situ. A subcutaneous vaccination strategy containing OVA-coupled anti-mDC-SIGN antibody generated antigen-specific polyfunctional CD8+ T cell and CD4+ T cell responses and a strong isotype-switched OVA-specific antibody response in vivo. We conclude that mDC-SIGN shows partly overlapping similarities to hDC-SIGN and that targeting mDC-SIGN provides a valuable approach to investigate the immunological function of DC-SIGN in vivo.
CD209a | SIGNR5 | Antigen delivery | Dendritic cell | Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin | Vaccination
Animals | Animals, Genetically Modified | Antibodies | CD4-Positive T-Lymphocytes | CD8-Positive T-Lymphocytes | Cell Adhesion Molecules | Dendritic Cells | Female | Granulocyte-Macrophage Colony-Stimulating Factor | Humans | Lectins, C-Type | Macrophages | Male | Mice | Mice, Inbred C57BL | Ovalbumin | Receptors, Cell Surface | Vaccination | Adaptive Immunity | Antigen Presentation
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