RETRACTED: Endocytic recycling and vesicular transport systems mediate transcytosis of Leptospira interrogans across cell monolayer
Yang Li,
Kai-Xuan Li,
Wei-Lin Hu,
David M Ojcius,
Jia-Qi Fang,
Shi-Jun Li,
Xu'ai Lin,
Jie Yan
Affiliations
Yang Li
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China; Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Kai-Xuan Li
Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China; Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Wei-Lin Hu
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China; Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
David M Ojcius
Department of Biomedical Sciences, Arthur Dugoni School of Dentistry, University of the Pacific, San Francisco, United States
Jia-Qi Fang
Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China; Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Shi-Jun Li
Institute of Communicable Disease Prevention and Control, Guizhou Provincial Centre for Disease Control and Prevention, Guiyang, China
Xu'ai Lin
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China; Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China; Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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.
