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Responses of human endothelial cells to pathogenic and non-pathogenic Leptospira species. PLoS Negl Trop Dis 2010 Dec 14;4(12):e918 PMID: 21179504 PMCID: PMC3001904

Pubmed ID

21179504

DOI

10.1371/journal.pntd.0000918

Abstract

Leptospirosis is a widespread zoonotic infection that primarily affects residents of tropical regions, but causes infections in animals and humans in temperate regions as well. The agents of leptospirosis comprise several members of the genus Leptospira, which also includes non-pathogenic, saprophytic species. Leptospirosis can vary in severity from a mild, non-specific illness to severe disease that includes multi-organ failure and widespread endothelial damage and hemorrhage. To begin to investigate how pathogenic leptospires affect endothelial cells, we compared the responses of two endothelial cell lines to infection by pathogenic versus non-pathogenic leptospires. Microarray analyses suggested that pathogenic L. interrogans and non-pathogenic L. biflexa triggered changes in expression of genes whose products are involved in cellular architecture and interactions with the matrix, but that the changes were in opposite directions, with infection by L. biflexa primarily predicted to increase or maintain cell layer integrity, while L. interrogans lead primarily to changes predicted to disrupt cell layer integrity. Neither bacterial strain caused necrosis or apoptosis of the cells even after prolonged incubation. The pathogenic L. interrogans, however, did result in significant disruption of endothelial cell layers as assessed by microscopy and the ability of the bacteria to cross the cell layers. This disruption of endothelial layer integrity was abrogated by addition of the endothelial protective drug lisinopril at physiologically relevant concentrations. These results suggest that, through adhesion of L. interrogans to endothelial cells, the bacteria may disrupt endothelial barrier function, promoting dissemination of the bacteria and contributing to severe disease manifestations. In addition, supplementing antibiotic therapy with lisinopril or derivatives with endothelial protective activities may decrease the severity of leptospirosis.

Author List

Martinez-Lopez DG, Fahey M, Coburn J

Author

Jenifer Coburn PhD Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-78650714951   24 Citations

MESH terms used to index this publication - Major topics in bold

Bacterial Adhesion
Bacterial Translocation
Endothelial Cells
Gene Expression Profiling
Host-Pathogen Interactions
Humans
Leptospira
Lisinopril
Microarray Analysis
jenkins-FCD Prod-332 f92a19b0ec5e8e1eff783fac390ec127e367c2b5