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Infect Immun. 2018 Dec 19;87(1). pii: e00654-18. doi: 10.1128/IAI.00654-18. Print 2019 Jan.

Yersinia pseudotuberculosis Exploits CD209 Receptors for Promoting Host Dissemination and Infection.

Author information

1
Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China.
2
Laboratory of Immunology, Brain Korea 21 PLUS Project for Medical Science, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
3
Department of Pathogen Biology and Immunology, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
4
Department of Paediatrics & Child Health, The University of Zambia-University College London Medical School at Zambia, Lusaka, Zambia.
5
Department of Biomedical Science, College of Medicine-Rockford, University of Illinois at Chicago, Rockford, Illinois, USA.
6
Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
7
Department of Diarrheal Diseases, National Institute for Communicable Diseases Control and Prevention, Beijing, China.
8
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
9
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
10
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
11
Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
12
Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland mikael.skurnik@helsinki.fi chentie@hust.edu.cn.
13
Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China mikael.skurnik@helsinki.fi chentie@hust.edu.cn.
#
Contributed equally

Abstract

Yersinia pseudotuberculosis is a Gram-negative enteropathogen and causes gastrointestinal infections. It disseminates from gut to mesenteric lymph nodes (MLNs), spleen, and liver of infected humans and animals. Although the molecular mechanisms for dissemination and infection are unclear, many Gram-negative enteropathogens presumably invade the small intestine via Peyer's patches to initiate dissemination. In this study, we demonstrate that Y. pseudotuberculosis utilizes its lipopolysaccharide (LPS) core to interact with CD209 receptors, leading to invasion of human dendritic cells (DCs) and murine macrophages. These Y. pseudotuberculosis-CD209 interactions result in bacterial dissemination to MLNs, spleens, and livers of both wild-type and Peyer's patch-deficient mice. The blocking of the Y. pseudotuberculosis-CD209 interactions by expression of O-antigen and with oligosaccharides reduces infectivity. Based on the well-documented studies in which HIV-CD209 interaction leads to viral dissemination, we therefore propose an infection route for Y. pseudotuberculosis where this pathogen, after penetrating the intestinal mucosal membrane, hijacks the Y. pseudotuberculosis-CD209 interaction antigen-presenting cells to reach their target destinations, MLNs, spleens, and livers.

KEYWORDS:

CD209a; CD209b; DC-SIGN; DCs; LPS core; SIGN-R1; Yersinia pseudotuberculosis; dendritic cells; dissemination; lipopolysaccharide core

PMID:
30348825
PMCID:
PMC6300620
[Available on 2019-06-19]
DOI:
10.1128/IAI.00654-18

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