In vitro association of leptospires with host cells

Thomas, D D; Higbie, L M

doi:10.1128/iai.58.3.581-585.1990

Cited by 64 publications

(36 citation statements)

References 8 publications

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“…Leptospires have a characteristic spiral shape and corkscrew motion, and these features are considered to relate with its pathogenicity for host tissue invasion (Barocchi et al 2002). Penetration of cells such as human umbilical vein endothelial cells, Madin-Darby canine kidney cells, Vero cells and macrophage by leptospires were reported in in vitro studies (Barocchi et al 2002;Merien et al 1997, Thomas & Higbie 1990. Therefore, we carefully investigated whether leptospires localized in hepatocytes using SEM.…”

Section: Discussionmentioning

confidence: 99%

Destruction of the hepatocyte junction by intercellular invasion of Leptospira causes jaundice in a hamster model of Weil's disease

Miyahara

Saito

Kanemaru

et al. 2014

Int J Experimental Path

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Weil's disease, the most severe form of leptospirosis, is characterized by jaundice, haemorrhage and renal failure. The mechanisms of jaundice caused by pathogenic Leptospira remain unclear. We therefore aimed to elucidate the mechanisms by integrating histopathological changes with serum biochemical abnormalities during the development of jaundice in a hamster model of Weil's disease. In this work, we obtained three-dimensional images of infected hamster livers using scanning electron microscope together with freeze-cracking and cross-cutting methods for sample preparation. The images displayed the corkscrew-shaped bacteria, which infiltrated the Disse's space, migrated between hepatocytes, detached the intercellular junctions and disrupted the bile canaliculi. Destruction of bile canaliculi coincided with the elevation of conjugated bilirubin, aspartate transaminase and alkaline phosphatase levels in serum, whereas serum alanine transaminase and γ-glutamyl transpeptidase levels increased slightly, but not significantly. We also found in ex vivo experiments that pathogenic, but not non-pathogenic leptospires, tend to adhere to the perijunctional region of hepatocyte couplets isolated from hamsters and initiate invasion of the intercellular junction within 1 h after co-incubation. Our results suggest that pathogenic leptospires invade the intercellular junctions of host hepatocytes, and this invasion contributes in the disruption of the junction. Subsequently, bile leaks from bile canaliculi and jaundice occurs immediately. Our findings revealed not only a novel pathogenicity of leptospires, but also a novel mechanism of jaundice induced by bacterial infection.

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Section: Discussionmentioning

confidence: 99%

Destruction of the hepatocyte junction by intercellular invasion of Leptospira causes jaundice in a hamster model of Weil's disease

Miyahara

Saito

Kanemaru

et al. 2014

Int J Experimental Path

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“…The adhesion of Leptospira to cultured mammalian cells was reported, and the efficiency of attachment was correlated with bacterial virulence (Thomas & Higbie, 1990).…”

Section: Leptospiral Adhesion To Ecmmentioning

confidence: 99%

Leptospiral extracellular matrix adhesins as mediators of pathogen-host interactions

Vieira

Fernandes

Domingos

et al. 2013

FEMS Microbiol Lett

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Leptospirosis is been considered an important infectious disease that affects humans and animals worldwide. This review summarizes our current knowledge of bacterial attachment to extracellular matrix (ECM) components and discusses the possible role of these interactions for leptospiral pathogenesis. Leptospiral proteins show different binding specificity for ECM molecules: some are exclusive laminin-binding proteins (Lsa24/LfhA/LenA, Lsa27), while others have broader spectrum binding profiles (LigB, Lsa21, LipL53). These proteins may play a primary role in the colonization of host tissues. Moreover, there are multifunctional proteins that exhibit binding activities toward a number of target proteins including plasminogen/plasmin and regulators of the complement system, and as such, might also act in bacterial dissemination and immune evasion processes. Many ECM-interacting proteins are recognized by human leptospirosis serum samples indicating their expression during infection. This compilation of data should enhance our understanding of the molecular mechanisms of leptospiral pathogenesis.

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“…Although little is known about how Leptospira species establish infection in their hosts, adhesion to the host cell surface and extracellular matrix (ECM) by pathogens is often the first critical step in the initiation of infection. Several groups have investigated the adhesion of Leptospira interrogans to endothelial, fibroblast, kidney epithelial, and monocyte-macrophage cell lines cultured in vitro [3][4][5][6][7][8][9]. It is likely that pathogenic leptospires can attach to several different types of mammalian receptors to establish the infection.…”

Section: Introductionmentioning

confidence: 99%

Responses of Human Endothelial Cells to Pathogenic and Non-Pathogenic Leptospira Species

2010

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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.

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In vitro association of leptospires with host cells

Cited by 64 publications

References 8 publications

Destruction of the hepatocyte junction by intercellular invasion of Leptospira causes jaundice in a hamster model of Weil's disease

Destruction of the hepatocyte junction by intercellular invasion of Leptospira causes jaundice in a hamster model of Weil's disease

Leptospiral extracellular matrix adhesins as mediators of pathogen-host interactions

Responses of Human Endothelial Cells to Pathogenic and Non-Pathogenic Leptospira Species

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