The relapsing fever spirochaete, Borrelia crocidurae, activates human endothelial cells and promotes the transendothelial migration of neutrophils

Shamaei-Tousi, Alireza; Burns, Margaret J.; Benach, Jorge L.; Furie, Martha B.; Gergel, Edna I.; Bergström, Sven

doi:10.1046/j.1462-5822.2000.00083.x

Cited by 21 publications

(13 citation statements)

References 42 publications

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“…The mechanism of vascular injury in spirochetal infections is not known. Outer membrane lipoproteins from spirochetes have been shown to activate endothelial cells to produce proinflammatory mediators (25,33,34,36,38 (27). This study confirms at the experimental level an important protective role for IL-10 in acute RF borreliosis in immunocompetent mice via prevention of hemorrhagic and thrombotic complications.…”

Section: Discussionsupporting

confidence: 72%

Relapsing Fever Borreliosis in Interleukin-10-Deficient Mice

et al. 2008

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Relapsing fever (RF) is a spirochetal infection characterized by periods of sickness with fever at time of high bacteremia that alternate with afebrile periods of relative well being during low bacteremia. Patients with epidemic RF who are doing relatively well have extraordinarily high levels of interleukin-10 (IL-10) in the circulation. We investigated the possibility that IL-10 plays an important protective role in this infection using wild-type and IL-10-deficient mice inoculated with virulent serotype 2 of the RF spirochete Borrelia turicatae. During peak bacteremia there was increased systemic production of IL-10 that quickly resolved in the postpeak period; in contrast, IL-6 and CXCL13 production increased during the peak but remained elevated during postpeak bacteremia. IL-10 deficiency resulted in lower bacteremia, increased specific antibody production, higher production of CXCL13 and IL-6, and thrombotic and hemorrhagic complications affecting multiple organs with secondary tissue injury. Our results revealed that production of IL-10 is highly regulated during RF and plays an important protective role in the prevention of hemorrhagic and thrombotic complications at the cost of reduced pathogen control.

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Section: Discussionsupporting

confidence: 72%

Relapsing Fever Borreliosis in Interleukin-10-Deficient Mice

et al. 2008

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“…Several previous studies have documented the ability of bacteria to activate endothelial cells (33)(34)(35)(36) and the prominent role that apoptosis plays in the interaction between pathogens and endothelial cells (37)(38)(39). However, there has been little research into the mechanisms involved in injury and protection of the cerebral microcirculation during bacteremia.…”

Section: Discussionmentioning

confidence: 99%

IL-10 Prevents Apoptosis of Brain Endothelium during Bacteremia

Londoño

Carvajal

Strle

et al. 2011

The Journal of Immunology

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IL‐10 deficient mice infected with the relapsing fever bacterium Borrelia turicatae rapidly succumb to brain hemorrhage if they are unable to clear peak bacteremia. Here we investigated the protective role of IL‐10 during relapsing‐remitting bacterial infection and explored the molecular events involved in protection of brain endothelium by IL‐10. The results showed that severe endothelial cell injury leading to hemorrhage in the brain and other organs occurred in IL‐10 deficient mice during relapsing‐remitting infection. Human brain microvascular endothelial cells (HBMEC) upon exposure to whole bacteria or purified bacterial lipoprotein are rapidly killed by apoptosis and produced abundant pro‐inflammatory mediators but did not produce any IL‐10. HBMEC apoptosis during exposure to low number of bacteria was associated with down regulation of TNF and TNFAIP3 and upregulation of BAX. In contrast, exposure to high concentrations of purified outer membrane lipoprotein was associated with dramatic upregulation of FAS, FAS ligand, and the adaptor molecules RIPK1 and CFLAR. Exogenous IL‐10 reversed all the apoptotic signaling changes induced by whole bacteria or purified lipoprotein. The results indicate that IL‐10 prevent brain endothelial cell injury and point to a prominent role for bacterial lipoprotein mediated activation of different apoptosis pathways in this process.

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“…Studies with the pathogenic spirochaetes Borrelia sp. and Treponema sp., reported the stimulation of the vascular endothelium in vitro that lead to the upregulation of CAMs (Sellati et al, 1995(Sellati et al, , 1996Lee et al, 2000Lee et al, , 2005Shamaei-Tousi et al, 2000). The genome sequencing of L. interrogans serovar Copenhageni revealed 263 predicted potential cell-surface-exposed membrane proteins (Nascimento et al, 2004a, b), but to date only a few have been characterized at the molecular level.…”

Section: Introductionmentioning

confidence: 99%

A novel leptospiral protein increases ICAM-1 and E-selectin expression in human umbilical vein endothelial cells

Vieira

D’Atri

Schattner

et al. 2007

FEMS Microbiology Letters

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It has been reported previously that activation of vascular endothelium by outer membrane proteins of the spirochetes Borrelia sp. and Treponema sp. resulted in enhanced expression of endothelial cell adhesion molecules. To investigate the role of leptospiral proteins in this process, a predicted lipoprotein encoded by the gene LIC10365 was selected, which belongs to a paralogous family that presents a domain of unknown function, DUF1565. The LIC10365 gene was cloned and the protein expressed in Escherichia coli C43 (DE3) strain using the vector pAE. The recombinant protein tagged with N-terminal hexahistidine was purified by metal-charged chromatography and was used to assess its ability to activate cultured human umbilical vein endothelial cells. The rLIC10365 activated endothelium in such a manner that E-selectin and intercellular adhesion molecule 1 (ICAM-1) became upregulated in a dose-dependent fashion. The LIC10365-encoded protein was identified in vivo in the renal tubules of animal during experimental infection with Leptospira interrogans. Collectively, these results implicate the LIC10365-coding protein of L. interrogans as a potential effector molecule in the promotion of a host inflammatory response. This is the first report of a leptospiral protein capable of up-regulating the expression of endothelial cell adhesion molecules ICAM-1 and E-selectin.

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The relapsing fever spirochaete, Borrelia crocidurae, activates human endothelial cells and promotes the transendothelial migration of neutrophils

Cited by 21 publications

References 42 publications

Relapsing Fever Borreliosis in Interleukin-10-Deficient Mice

Relapsing Fever Borreliosis in Interleukin-10-Deficient Mice

IL-10 Prevents Apoptosis of Brain Endothelium during Bacteremia

A novel leptospiral protein increases ICAM-1 and E-selectin expression in human umbilical vein endothelial cells

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