Endocytic recycling and vesicular transport systems mediate transcytosis of Leptospira interrogans across cell monolayer
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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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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.
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).
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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- Genetics and Genomics
- Microbiology and Infectious Disease
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