Delayed Invasion of the Kidney and Brain by<i>Borrelia crocidurae</i>in Plasminogen-Deficient Mice

Nordstrand, Annika; Shamaei-Tousi, Alireza; Ny, Annelii; Bergström, Sven

doi:10.1128/iai.69.9.5832-5839.2001

Cited by 62 publications

(53 citation statements)

References 36 publications

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“…Examination of the spinal cord revealed a severe infiltration of immune cells in the lumbar sections. We have identified T cells as the essential contributors for the induction of the CNS disease, distinguishing the current findings from those previously described studies in RF (3,4,13,14,29). Although the B. hermsii infection-associated neurologic symptoms were remarkably similar to those of classical EAE, Luxol fast blue staining of spinal cord sections did not reveal demyelination (data not shown), a hallmark of EAE, indicating that B. hermsii-induced CNS pathogenesis is different from classical EAE.…”

Section: Discussioncontrasting

confidence: 40%

“…In the B. crocidurae RF model, macrophages are the most dominant cell type among the infiltrating immune cells in the brain (4,29). The perivascular infiltrates during Spanish RF Borrelia infection are composed primarily of B cells, plasma cells, and monocytes, but rarely of CD4 and CD8 cells, and meningitis develops after 17 d but no neurologic disease manifestations have been reported (3,13).…”

Section: Discussionmentioning

confidence: 99%

“…For example, in the epidemic form of RF due to B. recurrentis, the incidence of CNS complications can be as high as 40%. The murine models for neurologic involvement during RF are characterized mainly by the presence of bacteria in the CNS and/or meningitis (4,(12)(13)(14).…”

mentioning

confidence: 99%

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Induction of Distinct Neurologic Disease Manifestations during Relapsing Fever Requires T Lymphocytes

Liu¹,

Fitzgerald

Gran

et al. 2010

The Journal of Immunology

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Relapsing fever borreliosis is a multisystemic infection characterized primarily by bacteremia but can extend to the CNS. The incidence of CNS disease manifestations in humans depends on the infecting relapsing fever Borrelia species. In the murine model of Borrelia hermsii infection we found high incidence of distinct signs of CNS disease that ranged from a flaccid tail to complete paralysis of hind limbs. Infiltration of large number of T cells into the spinal cord of B. hermsii-infected mice and the upregulation of MHC class II and CD80 on infiltrating macrophages and on microglial cells suggested a role for T cell and Ag-presenting cell interactions in this pathogenesis. Indeed, B. hermsii infection did not induce CNS disease manifestations in T cell-deficient mice (TCR-β × δ−/−), although it resulted in bacteremia comparable to wild-type (Wt) level. Moreover, the infiltration of immune cells into the spinal cord of TCR-β × δ−/− mice was reduced and the resident microglial cells were not activated. Histopathological analysis of lumbar sections of the spinal cord confirmed severe inflammation in Wt but not in TCR-β × δ−/− mice. Induction of CNS disease was dependent on the B. hermsii strain as well as on the ability of the host to control bacteremia. Mice that are impaired in controlling B. hermsii, such as CD14−/− mice, exhibited more severe CNS disease than Wt mice. This study demonstrates that distinct neurologic disease manifestations develop during relapsing fever and that T cells play a critical role in the induction of neuropathogenesis.

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Section: Discussioncontrasting

confidence: 40%

Section: Discussionmentioning

confidence: 99%

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Induction of Distinct Neurologic Disease Manifestations during Relapsing Fever Requires T Lymphocytes

Liu¹,

Fitzgerald

Gran

et al. 2010

The Journal of Immunology

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“…and Treponema denticola with possible implications for pathogenesis. 41,[49][50][51][52] PLA is a serine protease that can degrade a large spectrum of substrates, including fibrin clots, connective tissue, and components of extracellular matrices. 53,54 Human PLG/PLA proteolytic activity was first described for Leptospira spp.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Three Novel Adhesins of Leptospira interrogans

Siqueira¹,

Atzingen²,

Alves³

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. We report cloning, expression, purification, and characterization of three predicted leptospiral membrane proteins (LIC11360, LIC11009, and LIC11975). In silico analysis and proteinase K accessibility data suggest that these proteins might be surface exposed. We show that proteins encoded by LIC11360, LIC11009 and LIC11975 genes interact with laminin in a dose-dependent and saturable manner. The proteins are referred to as leptospiral surface adhesions 23, 26, and 36 (Lsa23, Lsa26, and Lsa36), respectively. These proteins also bind plasminogen and generate active plasmin. Attachment of Lsa23 and Lsa36 to fibronectin occurs through the involvement of the 30-kDa and 70-kDa heparin-binding domains of the ligand. Dose-dependent, specific-binding of Lsa23 to the complement regulator C4BP and to a lesser extent, to factor H, suggests that this protein may interfere with the complement cascade pathways. Leptospira spp. may use these interactions as possible mechanisms during the establishment of infection.

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“…The subsequent activation of plasminogen to plasmin may contribute to the virulence of these microorganisms (13). However, during bacterial arthritis, plasmin may also be of importance in the host defense by degrading deleterious bacteria or ECM components during tissue repair (14).…”

mentioning

confidence: 99%

Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus–induced arthritis

Guo¹,

Li²,

Hagström³

et al. 2008

Arthritis & Rheumatism

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Objective. To assess the functional roles of plasmin in a murine model of Staphylococcus aureus-induced bacterial arthritis.Methods. Bacterial arthritis was induced in plasminogen-deficient (Plg -/-) and wild-type (Plg ؉/؉ ) littermates by local injection of 1 ؋ 10 6 colony-forming units of S aureus into the knee joints. Human plasminogen was administered to Plg -/-mice on days 0-7 or days 7-14. Antibiotic treatment was administered to Plg -/-mice on days 7-14. Bacteria counts and histologic, immunohistochemical, and Western blot analyses were performed.Results. In Plg ؉/؉ mice, S aureus counts had declined within 2 days, and by day 28 the bacteria had been completely eliminated. However, S aureus was still detectable in all injected joints from Plg -/-mice, and bacteria counts were 27 times higher than the amount injected on day 0. The extent of macrophage and neutrophil recruitment to the infected joints was comparable for Plg ؉/؉ and Plg -/-mice on days 1, 7, and 14. The activation of these inflammatory cells appeared to be impaired in Plg -/-mice, however. Treatment of Plg -/-mice with antibiotic (cloxacillin) resulted in successful killing of the bacteria, but the necrotic tissue remained in the infected joints. When human plasminogen was given intravenously to Plg -/-mice daily for 7 days, bacterial clearance was greatly improved as compared with their untreated counterparts, and the amount of necrotic tissue in the joint cavity was dramatically reduced. The expression of interleukin 6 (IL-6) and IL-10 was higher in Plg ؉/؉ mice than in Plg -/-mice during bacterial arthritis.Conclusion. Our findings indicate that plasmin plays a pluripotent role in protecting against S aureusinduced arthritis by activating inflammatory cells, killing bacteria, removing necrotic tissue, and enhancing cytokine expression.Staphylococcus aureus is the microorganism most frequently associated with bacterial arthritis (1,2), which results in synovial inflammation, cartilage and bone destruction, and eventually, joint deformity (3). The plasminogen activator (PA) system is a general proteolytic system that has been suggested to play an important role in the development of different types of arthritis (4-6). Plasminogen can be activated to the broadspectrum protease plasmin by either of the 2 physiologic PAs, tissue-type PA (tPA) or urokinase-type PA (uPA). In addition to its function in fibrinolysis, plasmin(ogen) plays a role in degradation of the extracellular matrix (ECM) and in tissue remodeling during many physiologic and pathologic processes, such as wound healing (7), tumor cell invasion, angiogenesis, and rheumatoid arthritis (RA) (8). There is some evidence that plasmin can also induce proinflammatory responses independently of its proteolytic properties (9).A number of pathogenic microorganisms have been shown to bind plasminogen (10-12). The subsequent activation of plasminogen to plasmin may contribute to the virulence of these microorganisms (13). However, during bacterial arthritis, plasmin may also be of importance...

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Delayed Invasion of the Kidney and Brain byBorrelia crociduraein Plasminogen-Deficient Mice

Cited by 62 publications

References 36 publications

Induction of Distinct Neurologic Disease Manifestations during Relapsing Fever Requires T Lymphocytes

Induction of Distinct Neurologic Disease Manifestations during Relapsing Fever Requires T Lymphocytes

Characterization of Three Novel Adhesins of Leptospira interrogans

Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus–induced arthritis

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