title: Human dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin (CD209) is a receptor for Yersinia pestis that promotes phagocytosis by dendritic cells.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, University of Illinois at Chicago (UIC), 1601 Parkview Avenue, Rockford, IL 61107, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.forename: Mikael
authors.initials: M
authors.lastname: Skurnik
authors.forename: Shu-Sheng
authors.initials: SS
authors.lastname: Zhang
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Kalyanasundaram
authors.forename: Silvia
authors.initials: S
authors.lastname: Bulgheresi
authors.forename: Johnny J
authors.initials: JJ
authors.lastname: He
authors.forename: John D
authors.initials: JD
authors.lastname: Klena
authors.forename: B Joseph
authors.initials: BJ
authors.lastname: Hinnebusch
authors.forename: Tie
authors.initials: T
authors.lastname: Chen
mesh_terms: D015815:Cell Adhesion Molecules / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000502:physiology*; D008070:Lipopolysaccharides / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000382:microbiology; D008954:Models, Biological; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000502:physiology*; D015010:Yersinia pestis / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin