Host Langerin (CD207) is a receptor for Yersinia pestis phagocytosis and promotes dissemination

Autoren:Yang, K (Huazhong University of Science and Technology); Park, CG (Yonsei University Seoul); Cheong, C (Institut de Recherches Cliniques de Montréal (IRCM)); Bulgheresi, Silvia; Zhang, Shusheng (University of Illinois at Chicago); Zhang, Pei (University of Illinois at Chicago); He, Y (Huazhong University of Science and Technology); Jiang, L (Huazhong University of Science and Technology); Huang, H (Huazhong University of Science and Technology); Ding, H (Huazhong University of Science and Technology); Wu, Y (Huazhong University of Science and Technology); Wang, S (Huazhong University of Science and Technology); Zhang, L (Huazhong University of Science and Technology); Li, A (Huazhong University of Science and Technology); Xia, L (National Institute for Communicable Diseases Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing); Bartra, SS (University of Miami); Plano, GV (University of Miami); Skurnik, M (University of Helsinki); Klena, J (Peking University); Chen, T (Huazhong University of Science and Technology)
Abstrakt: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.
Journaltitel:Immunology and cell biology
Peer reviewed:true
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