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Originally published In Press as doi:10.1074/jbc.M804646200 on July 23, 2008

J. Biol. Chem., Vol. 283, Issue 46, 31511-31521, November 14, 2008
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Plasminogen Activator Pla of Yersinia pestis Utilizes Murine DEC-205 (CD205) as a Receptor to Promote Dissemination*

Shu-sheng Zhang{ddagger}, Chae Gyu Park§1, Pei Zhang{ddagger}, Sara Schesser Bartra§§, Gregory V. Plano, John D. Klena||, Mikael Skurnik**, B. Joseph Hinnebusch{ddagger}{ddagger}, and Tie Chen{ddagger}2

From the {ddagger}Department of Biomedical Sciences, College of Medicine-Rockford, University of Illinois at Chicago, Rockford, Illinois 61107, §Laboratory of Cellular Physiology and Immunology, Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, New York 10065, Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida 33101, ||School of Biological Sciences, University of Canterbury, Christchurch, New Zealand, **Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki and Helsinki University Central Hospital Laboratory Diagnostics, Helsinki 00014, Finland, {ddagger}{ddagger}Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Minnesota 59840, and §§Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden

Yersinia pestis, a Gram-negative bacterium that causes bubonic and pneumonic plague, is able to rapidly disseminate to other parts of its mammalian hosts. Y. pestis expresses plasminogen activator (PLA) on its surface, which has been suggested to play a role in bacterial dissemination. It has been speculated that Y. pestis hijacks antigen-presenting cells, such as macrophages (M{Phi}s) and dendritic cells, to be delivered to lymph nodes to initiate dissemination and infection. Both alveolar M{Phi}s and pulmonary dendritic cells express a C-type lectin receptor, DEC-205 (CD205), which mediates antigen uptake and presentation. However, no ligand has been identified for DEC-205. In this study, we show that the invasion of alveolar M{Phi}sby Y. pestis depends both in vitro and in vivo on the expression of PLA. DEC-205-expressing M{Phi}s and transfectants, but not their negative counterparts, phagocytosed PLA-expressing Y. pestis and Escherichia coli K12 more efficiently than PLA-negative controls. The interactions between PLA-expressing bacteria and DEC-205-expressing transfectants or alveolar M{Phi}s could be inhibited by an anti-DEC-205 antibody. Importantly, the blockage of the PLA-DEC-205 interaction reduced the dissemination of Y. pestis in mice. In conclusion, murine DEC-205 is a receptor for PLA of Y. pestis, and this host-pathogen interaction appears to play a key role in promoting bacterial dissemination.


Received for publication, June 18, 2008 , and in revised form, July 14, 2008.

* This work was supported, in whole or in part, by National Institutes of Health grants (USPHS). This work was also supported in part by a grant from the University of Illinois, College of Medicine, Rockford (to T. C.), and work in the Skurnik laboratory was supported by Academy of Finland Grant 114075. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Supported by National Institutes of Health Grant AI 057158 (Northeast Biodefense Center).

2 To whom correspondence should be addressed: Dept. of Biomedical Sciences, College of Medicine-Rockford, University of Illinois at Chicago, 1601 Parkview Ave., Rockford, IL 61107. Tel.: 815-395-5893; Fax: 815-395-5666; E-mail: tiechen{at}uic.edu.


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