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Human Dendritic Cell-Specific Intercellular Adhesion Molecule-Grabbing Nonintegrin (CD209) Is a Receptor for Yersinia pestis That Promotes Phagocytosis by Dendritic Cells

Department of Biomedical Sciences, College of Medicine, University of Illinois at Chicago (UIC), 1601 Parkview Avenue, Rockford, Illinois 61107,¹ Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki and Helsinki University Central Hospital Laboratory Diagnostics, Helsinki 00014, Finland,² Virus and Immunity Group in the Department of Virology, Institut Pasteur, Paris, France,³ Faculty of Life Sciences, Department of Marine Biology, University of Vienna, Vienna, Austria,⁴ Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202,⁵ School of Biological Sciences, University of Canterbury, Christchurch, New Zealand,⁶ Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, Montana 59840⁷

Received 11 September 2007/ Returned for modification 22 October 2007/ Accepted 29 January 2008

Yersinia pestis is the etiologic agent of bubonic and pneumonic plagues. It is speculated that Y. pestis hijacks antigen-presenting cells (APCs), such as dendritic cells (DCs) and alveolar macrophages, in order to be delivered to lymph nodes. However, how APCs initially capture the bacterium remains uncharacterized. It is well known that HIV-1 uses human DC-specific intercellular adhesion molecule-grabbing nonintegrin (DC-SIGN) (CD209) receptor, expressed by APCs, to be captured and delivered to target cell, such as CD4⁺ lymphocytes. Several gram-negative bacteria utilize their core lipopolysaccharides (LPS) as ligands to interact with the human DC-SIGN. Therefore, it is possible that Y. pestis, whose core LPS is naturally exposed, might exploit DC-SIGN to invade APCs. We demonstrate in this study that Y. pestis directly interacts with DC-SIGN and invades both DCs and alveolar macrophages. In contrast, when engineered to cover the core LPS, Y. pestis loses its ability to invade DCs, alveolar macrophages, and DC-SIGN-expressing transfectants. The interaction between Y. pestis and human DCs can be reduced by a combination treatment with anti-CD209 and anti-CD207 antibodies. This study shows that human DC-SIGN is a receptor for Y. pestis that promotes phagocytosis by DCs in vitro.

Published ahead of print on 19 February 2008.

Editor: J. B. Bliska