Abstract |
Dendritic cells (DC), professional Ag-presenting cells located in mucosae and lymphoid organs, operate at the interface of innate and adaptive immunity and are likely the first cells to encounter invading HIV-1. Although the C-type lectin DC-Specific ICAM-3-grabbing non- integrin ( DC-SIGN) binds to several viruses, including HIV-1, its direct involvement in viral entry remains controversial. Despite its central role in DC function, little is known about the underlying molecular mechanism(s) of DC-SIGN-mediated Ag uptake. Here, we analyzed the early stages of DC-SIGN-mediated endocytosis and demonstrate that both membrane cholesterol and dynamin are required. Confocal microscopy and clathrin RNAi showed that DC-SIGN-mediated internalization occurs via clathrin-coated pits. Electron microscopy of ultrathin sections showed the involvement of DC-SIGN in clathrin-dependent HIV-1 internalization by DC. Currently, DC-specific C-type lectins are considered potential target in anti- tumor clinical trials. Detailed information about how different Ag are internalized via these receptors will facilitate the rational design of targeted therapeutic strategies.
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Authors | Alessandra Cambi, Inge Beeren, Ben Joosten, Jack A Fransen, Carl G Figdor |
Journal | European journal of immunology
(Eur J Immunol)
Vol. 39
Issue 7
Pg. 1923-8
(Jul 2009)
ISSN: 1521-4141 [Electronic] Germany |
PMID | 19585517
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens
- Cell Adhesion Molecules
- Clathrin
- DC-specific ICAM-3 grabbing nonintegrin
- Lectins, C-Type
- RNA, Small Interfering
- Receptors, Cell Surface
- Cholesterol
- Dynamins
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Topics |
- Animals
- Antigens
(metabolism)
- CHO Cells
- Cell Adhesion Molecules
(genetics, metabolism)
- Cell Membrane
(metabolism)
- Cholesterol
(metabolism)
- Clathrin
(genetics, metabolism)
- Cricetinae
- Cricetulus
- Dendritic Cells
(cytology, metabolism, ultrastructure)
- Dynamins
(genetics, metabolism)
- Endocytosis
- HIV-1
(metabolism)
- Humans
- Lectins, C-Type
(genetics, metabolism)
- Microscopy, Confocal
- Microscopy, Electron
- RNA, Small Interfering
(genetics)
- Receptors, Cell Surface
(genetics, metabolism)
- Solubility
- Transfection
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