Human dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin (CD209) is a receptor for Yersinia pestis that promotes phagocytosis by dendritic cells.
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.
Zhang
Pei
P
Department of Biomedical Sciences, College of Medicine, University of Illinois at Chicago (UIC), 1601 Parkview Avenue, Rockford, IL 61107, USA.
Skurnik
Mikael
M
Zhang
Shu-Sheng
SS
Schwartz
Olivier
O
Kalyanasundaram
Ramaswamy
R
Bulgheresi
Silvia
S
He
Johnny J
JJ
Klena
John D
JD
Hinnebusch
B Joseph
BJ
Chen
Tie
T
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
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin