The Urokinase Receptor Can Be Induced by<i>Borrelia burgdorferi</i>through Receptors of the Innate Immune System

Coleman, James L.; Benach, Jorge L.

doi:10.1128/iai.71.10.5556-5564.2003

Cited by 32 publications

(32 citation statements)

References 75 publications

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“…B. burgdorferi (8,25) and Borrelia crocidurae (63) spirochetes use the fibrinolytic system to disseminate into host tissues, including the brain. At the same time B. burgdorferi induces the expres-sion and secretion of the urokinase-type plasminogen activator (uPA) and expression of the uPA receptor (uPAR) by a variety of cell types, including monocytes (10,12). As the fibrinolytic system can directly digest components of the extracellular matrix (11), it can also activate other proteases, including matrix metalloproteinases (MMPs).…”

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confidence: 99%

Borrelia burgdorferi, Host-Derived Proteases, and the Blood-Brain Barrier

Grab¹,

et al. 2005

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Neurological manifestations of Lyme disease in humans are attributed in part to penetration of the blood-brain barrier (BBB) and invasion of the central nervous system (CNS) by Borrelia burgdorferi. However, how the spirochetes cross the BBB remains an unresolved issue. We examined the traversal of B. burgdorferi across the human BBB and systemic endothelial cell barriers using in vitro model systems constructed of human brain microvascular endothelial cells (BMEC) and EA.hy 926, a human umbilical vein endothelial cell (HUVEC) line grown on Costar Transwell inserts. These studies showed that B. burgdorferi differentially crosses human BMEC and HUVEC and that the human BMEC form a barrier to traversal. During the transmigration by the spirochetes, it was found that the integrity of the endothelial cell monolayers was maintained, as assessed by transendothelial electrical resistance measurements at the end of the experimental period, and that B. burgdorferi appeared to bind human BMEC by their tips near or at cell borders, suggesting a paracellular route of transmigration. Importantly, traversal of B. burgdorferi across human BMEC induces the expression of plasminogen activators, plasminogen activator receptors, and matrix metalloproteinases. Thus, the fibrinolytic system linked by an activation cascade may lead to focal and transient degradation of tight junction proteins that allows B. burgdorferi to invade the CNS.

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Borrelia burgdorferi, Host-Derived Proteases, and the Blood-Brain Barrier

Grab¹,

et al. 2005

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“…burgdorferi triggers the production of inflammatory mediators in macrophages via recognition of both Toll-like receptors (TLRs) and non-TLRs (8,12,22,71,78,95,97). In the present study, gene array analysis identified candidate genes from multiple pathways induced by live spirochetes that were a A corrected one-way analysis of variance was used to analyze the microarray data.…”

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Interleukin-10 Alters Effector Functions of Multiple Genes Induced by Borrelia burgdorferi in Macrophages To Regulate Lyme Disease Inflammation

et al. 2011

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“…As mentioned above, these spirochetes can fix plasmin onto their OMs, but they can also stimulate cells of the innate immune response to produce PLG activators (19,20,32,42,46) and modulate PLG activation inhibitors (39). In a similar manner, borreliae are important stimulators for the production of matrix metalloproteinases as part of their proinflammatory repertoire (34,35,43).…”

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The Enolase of Borrelia burgdorferi Is a Plasminogen Receptor Released in Outer Membrane Vesicles

et al. 2012

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The agent of Lyme disease, Borrelia burgdorferi, has a number of outer membrane proteins that are differentially regulated during its life cycle. In addition to their physiological functions in the organism, these proteins also likely serve different functions in invasiveness and immune evasion. In borreliae, as well as in other bacteria, a number of membrane proteins have been implicated in binding plasminogen. The activation and transformation of plasminogen into its proteolytically active form, plasmin, enhances the ability of the bacteria to disseminate in the host. Outer membrane vesicles of B. burgdorferi contain enolase, a glycolytic-cycle enzyme that catalyzes 2-phosphoglycerate to form phosphoenolpyruvate, which is also a known plasminogen receptor in Gram-positive bacteria. The enolase was cloned, expressed, purified, and used to generate rabbit antienolase serum. The enolase binds plasminogen in a lysine-dependent manner but not through ionic interactions. Although it is present in the outer membrane, microscopy and proteinase K treatment showed that enolase does not appear to be exposed on the surface. However, enolase in the outer membrane vesicles is accessible to proteolytic degradation by proteinase K. Samples from experimentally and tick-infected mice and rabbits as well as from Lyme disease patients exhibit recognition of enolase in serologic assays. Thus, this immunogenic plasminogen receptor released in outer membrane vesicles could be responsible for external proteolysis in the pericellular environment and have roles in nutrition and in enhancing dissemination.

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The Urokinase Receptor Can Be Induced byBorrelia burgdorferithrough Receptors of the Innate Immune System

Abstract: Monocytic cells exposed to

Cited by 32 publications

References 75 publications

Borrelia burgdorferi, Host-Derived Proteases, and the Blood-Brain Barrier

Borrelia burgdorferi, Host-Derived Proteases, and the Blood-Brain Barrier

Interleukin-10 Alters Effector Functions of Multiple Genes Induced by Borrelia burgdorferi in Macrophages To Regulate Lyme Disease Inflammation

The Enolase of Borrelia burgdorferi Is a Plasminogen Receptor Released in Outer Membrane Vesicles

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