1. Microbiology and Infectious Disease

Endocytic recycling and vesicular transport systems mediate transcytosis of Leptospira interrogans across cell monolayer

  1. Yang Li
  2. Kai-Xuan Li
  3. Wei-Lin Hu
  4. David M Ojcius
  5. Jia-Qi Fang
  6. Shi-Jun Li
  7. Xu'ai Lin  Is a corresponding author
  8. Jie Yan  Is a corresponding author
  1. Zhejiang University, China
  2. Zhejiang University School of Medicine, China
  3. University of the Pacific, Arthur Dugoni School of Dentistry, United States
  4. Guizhou Provincial Centre for Disease Control and Prevention, China
https://doi.org/10.7554/eLife.44594
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Cite this article
  1. Yang Li
  2. Kai-Xuan Li
  3. Wei-Lin Hu
  4. David M Ojcius
  5. Jia-Qi Fang
  6. Shi-Jun Li
  7. Xu'ai Lin
  8. Jie Yan
(2019)
Endocytic recycling and vesicular transport systems mediate transcytosis of Leptospira interrogans across cell monolayer
eLife 8:e44594.
https://doi.org/10.7554/eLife.44594
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Abstract

Many bacterial pathogens can cause septicemia and spread from the bloodstream into internal organs. During leptospirosis, individuals are infected by contact with Leptospira-containing animal urine-contaminated water. The spirochetes invade internal organs after septicemia to cause disease aggravation, but the mechanism of leptospiral excretion and spreading remains unknown. Here, we demonstrated that Leptospira interrogans entered human/mouse endothelial and epithelial cells and fibroblasts by caveolae/integrin-β1-PI3K/FAK-mediated microfilament-dependent endocytosis to form Leptospira (Lep)-vesicles that did not fuse with lysosomes. Lep-vesicles recruited Rab5/Rab11 and Sec/Exo-SNARE proteins in endocytic recycling and vesicular transport systems for intracellular transport and release by SNARE-complex/FAK-mediated microfilament/microtubule-dependent exocytosis. Both intracellular leptospires and infected cells maintained their viability. Leptospiral propagation was only observed in mouse fibroblasts. Our study revealed that L. interrogans utilizes endocytic recycling and vesicular transport systems for transcytosis across endothelial or epithelial barrier in blood vessels or renal tubules, which contributes to spreading in vivo and transmission of leptospirosis.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Yang Li

    Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Kai-Xuan Li

    Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Wei-Lin Hu

    Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  4. David M Ojcius

    Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Jia-Qi Fang

    Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Shi-Jun Li

    Institute of Communicable Disease Prevention and Control, Guizhou Provincial Centre for Disease Control and Prevention, Guiyang, China
    Competing interests
    The authors declare that no competing interests exist.

  7. Xu'ai Lin

    Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
    For correspondence
    lxai122@163.com
    Competing interests
    The authors declare that no competing interests exist.

  8. Jie Yan

    Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
    For correspondence
    med_bp@zju.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2054-6986

Funding

National Natural Science Foundation of China (81671974)

  • Jie Yan

National Natural Science Foundation of China (81471907)

  • Jie Yan

National Natural Science Foundation of China (81501713)

  • Wei-Lin Hu

National Natural Science Foundation of China (81760366)

  • Shi-Jun Li

Program of High Level Creative Talents Cultivation in Guizhou Province of China (Qian Ke He Talent (2016) 4021)

  • Shi-Jun Li

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Reinhard Jahn, Max Planck Institute for Biophysical Chemistry, Germany

Ethics

Animal experimentation: All animals were handled in strict accordance with good animal practice as defined by the National Regulations for the Administration of Experimental Animals of China (1988-002) and the National Guidelines for Experimental Animal Welfare of China (2006-398).

Version history

  1. Received: December 20, 2018
  2. Accepted: April 18, 2019
  3. Accepted Manuscript published: April 23, 2019 (version 1)
  4. Version of Record published: May 13, 2019 (version 2)

Copyright

© 2019, Li et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Yang Li
  2. Kai-Xuan Li
  3. Wei-Lin Hu
  4. David M Ojcius
  5. Jia-Qi Fang
  6. Shi-Jun Li
  7. Xu'ai Lin
  8. Jie Yan
(2019)
Endocytic recycling and vesicular transport systems mediate transcytosis of Leptospira interrogans across cell monolayer
eLife 8:e44594.
https://doi.org/10.7554/eLife.44594

Share this article

https://doi.org/10.7554/eLife.44594

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