title: Host Langerin (CD207) is a receptor for Yersinia pestis phagocytosis and promotes dissemination.
abstract: Yersinia pestis is a Gram-negative bacterium that causes plague. After Y. pestis overcomes the skin barrier, it encounters antigen-presenting cells (APCs), such as Langerhans and dendritic cells. They transport the bacteria from the skin to the lymph nodes. However, the molecular mechanisms involved in bacterial transmission are unclear. Langerhans cells (LCs) express Langerin (CD207), a calcium-dependent (C-type) lectin. Furthermore, Y. pestis possesses exposed core oligosaccharides. In this study, we show that Y. pestis invades LCs and Langerin-expressing transfectants. However, when the bacterial core oligosaccharides are shielded or truncated, Y. pestis propensity to invade Langerhans and Langerin-expressing cells decreases. Moreover, the interaction of Y. pestis with Langerin-expressing transfectants is inhibited by purified Langerin, a DC-SIGN (DC-specific intercellular adhesion molecule 3 grabbing nonintegrin)-like molecule, an anti-CD207 antibody, purified core oligosaccharides and several oligosaccharides. Furthermore, covering core oligosaccharides reduces the mortality associated with murine infection by adversely affecting the transmission of Y. pestis to lymph nodes. These results demonstrate that direct interaction of core oligosaccharides with Langerin facilitates the invasion of LCs by Y. pestis. Therefore, Langerin-mediated binding of Y. pestis to APCs may promote its dissemination and infection.
authors.affiliation: Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: Laboratory of Immunology, Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Chae G
authors.initials: CG
authors.lastname: Park
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec, Canada.
authors.forename: Cheolho
authors.initials: C
authors.lastname: Cheong
authors.affiliation: Department of Ecogenomics and Systems Biology, University of Vienna, Vienna, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bulgheresi
authors.affiliation: Department of Biomedical Science, University of Illinois at Chicago, Rockford, IL, USA.
authors.forename: Shusheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Science, University of Illinois at Chicago, Rockford, IL, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: The Center for Experimental Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Honghui
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Shaogang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Animal Experimental Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Anyi
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Zoonotic Diseases, National Institute for Communicable Diseases Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Lianxu
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Sara S
authors.initials: SS
authors.lastname: Bartra
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Plano
authors.affiliation: Department of Bacteriology and Immunology, Research Programs Unit, Immunobiology, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Mikael
authors.initials: M
authors.lastname: Skurnik
authors.affiliation: The School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: John D
authors.initials: JD
authors.lastname: Klena
authors.affiliation: Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Tie
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000382:microbiology; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D001422:Bacterial Adhesion / Q000276:immunology; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D019081:O Antigens / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D010930:Plague / Q000276:immunology / Q000382:microbiology; D011485:Protein Binding / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D016019:Survival Analysis; D015010:Yersinia pestis / Q000276:immunology* / Q000378:metabolism / Q000502:physiology
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D019081:O Antigens; D011956:Receptors, Cell Surface
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