Human DC-SIGN (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 Ave., Rockford, IL 61107, USA; Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki and Helsinki University Central Hospital Laboratory Diagnostics, Helsinki 00014, Finland; Virus and Immunity Group in the Department of Virology, Institut Pasteur, France; Faculty of Life Sciences, Department of Marine Biology, University of Vienna, Austria; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; School of Biological Sciences, University of Canterbury, Christchurch, New Zealand; Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, NIH, NIAID, 903 South 4th Street Hamilton, MT 59840, USA

^* To whom correspondence should be addressed. Email: tiechen{at}uic.edu.

	Abstract

Yersinia pestis is the etiologic agent of bubonic and pneumonic plague. 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-SIGN (CD209) receptor, expressed by APCs, to be captured and delivered to target cells such as CD4⁺ lymphocytes. Several Gram-negative bacteria utilize their core lipopolysaccharide (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 of anti-CD209 and anti-CD207 antibodies. This study shows that human DC-SIGN is a receptor for Y. pestis that promotes phagocytosis by dendritic cells in vitro.