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Internalization of Leptospira interrogans via diverse endocytosis mechanisms in human macrophages and vascular endothelial cells
Leptospirosis, one of the leading global causes of morbidity and mortality, is an emerging public health problem, particularly in large urban centers of developing countries. Leptospirosis results from infection with an organism belonging to the Leptospira genus L. interrogans. The extensive invasiv...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531806/ https://www.ncbi.nlm.nih.gov/pubmed/36137081 http://dx.doi.org/10.1371/journal.pntd.0010778 |
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author | Zhao, Xin Guo, Jun Jia, Xiaoyuan Yang, Yaling Liu, Lijuan Nie, Weizhong Fang, Zhiqiang |
author_facet | Zhao, Xin Guo, Jun Jia, Xiaoyuan Yang, Yaling Liu, Lijuan Nie, Weizhong Fang, Zhiqiang |
author_sort | Zhao, Xin |
collection | PubMed |
description | Leptospirosis, one of the leading global causes of morbidity and mortality, is an emerging public health problem, particularly in large urban centers of developing countries. Leptospirosis results from infection with an organism belonging to the Leptospira genus L. interrogans. The extensive invasive ability has previously been documented, however a mechanism that describes how the organism is internalized by human macrophages and transmigrates through human blood vessel remains poorly understood. In the present study, we utilized a human macrophage and vascular endothelial cell line to study the diverse invasive mechanisms by which L. interrogans infections occur. We found that THP-1 and HUVEC had a diverse expression of cell receptors and L. interrogans entered THP-1 and HUVEC by different pathways. In the macrophage model cell line, ITGB1/FAK-signaling mediated microfilament dependent endocytosis with lysosome fusion, whereas ITGB1/CAV-1/PI3K-signaling mediated microfilament dependent endocytosis and transcytosis without lysosome fusion in the endothelial cell model. Shedding of pathogenic leptospires from HUVEC displayed higher viability than those from THP-1. The monolayer of HUVEC maintained integrity during the infection, while 3D imaging showed that leptospires were transmigrated both intra- and intercellularly. These results indicate that endocytosis of leptospires in human macrophages and human vascular endothelial cells are quite different, macrophages are responsible for eliminating leptospires in the human body during the infection while vascular endothelial cells facilitate dissemination of leptospires from blood vessels into target organs where they cause injury. |
format | Online Article Text |
id | pubmed-9531806 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-95318062022-10-05 Internalization of Leptospira interrogans via diverse endocytosis mechanisms in human macrophages and vascular endothelial cells Zhao, Xin Guo, Jun Jia, Xiaoyuan Yang, Yaling Liu, Lijuan Nie, Weizhong Fang, Zhiqiang PLoS Negl Trop Dis Research Article Leptospirosis, one of the leading global causes of morbidity and mortality, is an emerging public health problem, particularly in large urban centers of developing countries. Leptospirosis results from infection with an organism belonging to the Leptospira genus L. interrogans. The extensive invasive ability has previously been documented, however a mechanism that describes how the organism is internalized by human macrophages and transmigrates through human blood vessel remains poorly understood. In the present study, we utilized a human macrophage and vascular endothelial cell line to study the diverse invasive mechanisms by which L. interrogans infections occur. We found that THP-1 and HUVEC had a diverse expression of cell receptors and L. interrogans entered THP-1 and HUVEC by different pathways. In the macrophage model cell line, ITGB1/FAK-signaling mediated microfilament dependent endocytosis with lysosome fusion, whereas ITGB1/CAV-1/PI3K-signaling mediated microfilament dependent endocytosis and transcytosis without lysosome fusion in the endothelial cell model. Shedding of pathogenic leptospires from HUVEC displayed higher viability than those from THP-1. The monolayer of HUVEC maintained integrity during the infection, while 3D imaging showed that leptospires were transmigrated both intra- and intercellularly. These results indicate that endocytosis of leptospires in human macrophages and human vascular endothelial cells are quite different, macrophages are responsible for eliminating leptospires in the human body during the infection while vascular endothelial cells facilitate dissemination of leptospires from blood vessels into target organs where they cause injury. Public Library of Science 2022-09-22 /pmc/articles/PMC9531806/ /pubmed/36137081 http://dx.doi.org/10.1371/journal.pntd.0010778 Text en © 2022 Zhao et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Zhao, Xin Guo, Jun Jia, Xiaoyuan Yang, Yaling Liu, Lijuan Nie, Weizhong Fang, Zhiqiang Internalization of Leptospira interrogans via diverse endocytosis mechanisms in human macrophages and vascular endothelial cells |
title | Internalization of Leptospira interrogans via diverse endocytosis mechanisms in human macrophages and vascular endothelial cells |
title_full | Internalization of Leptospira interrogans via diverse endocytosis mechanisms in human macrophages and vascular endothelial cells |
title_fullStr | Internalization of Leptospira interrogans via diverse endocytosis mechanisms in human macrophages and vascular endothelial cells |
title_full_unstemmed | Internalization of Leptospira interrogans via diverse endocytosis mechanisms in human macrophages and vascular endothelial cells |
title_short | Internalization of Leptospira interrogans via diverse endocytosis mechanisms in human macrophages and vascular endothelial cells |
title_sort | internalization of leptospira interrogans via diverse endocytosis mechanisms in human macrophages and vascular endothelial cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531806/ https://www.ncbi.nlm.nih.gov/pubmed/36137081 http://dx.doi.org/10.1371/journal.pntd.0010778 |
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