Resistance to Lyme disease in decorin-deficient mice

Brown, Eric L.; Wooten, R. Mark; Johnson, Barbara J. B.; Iozzo, Renato V.; Smith, Amanda Paige; Dolan, Marc C.; Guo, Betty P.; Weis, Janis J.; Höök, Magnus

doi:10.1172/jci11692

Cited by 127 publications

(114 citation statements)

References 46 publications

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“…However, epithelial cell attachment by this strain could not be inhibited by exogenous decorin, and attempts to detect decorin in extracts of 293 cells by immunoblotting was inconclusive due to the poor sensitivity of commercially available anti-decorin antibody (J.R.F., unpublished observation). B. burgdorferi shows only a mild colonization defect in the joints of decorin-deficient mice, and it has been postulated that other proteoglycans, perhaps with structural similarity to decorin, are also recognized by DbpA or DbpB and promote attachment of B. burgdorferi (26).…”

Section: Discussionmentioning

confidence: 99%

“…Decorinbinding activity may promote tissue colonization during infection of the mammalian host, because the joints of decorindeficient mice are not as efficiently colonized by B. burgdorferi as joints of wild-type mice (26). In addition, dbpA and dbpB, which comprise a single operon on the linear plasmid lp54 (54), are expressed by B. burgdorferi in mammalian tissues, and the surface expression of both DbpA and DbpB is enhanced after host adaptation (25,27).…”

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confidence: 99%

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Decorin-binding proteins A and B confer distinct mammalian cell type-specific attachment by Borrelia burgdorferi , the Lyme disease spirochete

Fischer

Parveen

Magoun

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

110

149

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Host cell binding is an essential step in colonization by many bacterial pathogens, and the Lyme disease agent, Borrelia burgdorferi, which colonizes multiple tissues, is capable of attachment to diverse cell types. Glycosaminoglycans (GAGs) are ubiquitously expressed on mammalian cells and are recognized by multiple B. burgdorferi surface proteins. We previously showed that B. burgdorferi strains differ in the particular spectrum of GAGs that they recognize, leading to differences in the cultured mammalian cell types that they efficiently bind. The molecular basis of these binding specificities remains undefined, due to the difficulty of analyzing multiple, potentially redundant cell attachment pathways and to the paucity of genetic tools for this pathogen. In the current study, we show that the expression of decorin-binding protein (

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Decorin-binding proteins A and B confer distinct mammalian cell type-specific attachment by Borrelia burgdorferi , the Lyme disease spirochete

Fischer

Parveen

Magoun

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

110

149

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“…Six-to 8-week-old Female C3H͞HeJ and BALB͞c mice were immunized s.c. with 100 l of containing adjuvant plus WT-OspA, FTK-OspA, EV-Ctrl, or adjuvant alone. Primary immunizations were prepared in complete Freund's adjuvant (CFA), whereas subsequent immunizations were made by using incomplete Freund's adjuvant (30). C3H͞HeJ mice were immunized on days 0, 14, and 28 with 10 g of each protein or EV-Ctrl.…”

Section: Methodsmentioning

confidence: 99%

“…In experiments using BALB͞c mice, vaccine efficacy was determined by harvesting and culturing the blood and tissues (ear, heart, bladder, and joints) 7 and 14 days post infection, respectively. Briefly, 50 l of blood or tissue samples were cultured in 6 ml of BSK for 2 weeks at 34°C in a CO 2 -enriched atmosphere by using a GasPak chamber (Becton Dickinson and Company, Franklin Lakes, NJ) and were assessed for the presence of Bb by darkfield microscopy (30).…”

Section: Methodsmentioning

confidence: 99%

An effective second-generation outer surface protein A-derived Lyme vaccine that eliminates a potentially autoreactive T cell epitope

Willett

Meyer

Brown

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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The antigenic component of a common Lyme disease vaccine is recombinant outer surface protein A (rOspA) of Borrelia burgdorferi (Bb), the causative agent of Lyme disease. Coincidentally, patients with chronic, treatment-resistant Lyme arthritis develop an immune response against OspA, whereas those with acute Lyme disease usually do not. Treatment-resistant Lyme arthritis occurs in a subset of Lyme arthritis patients and is linked to HLA.DRB1*0401 (DR4) and related alleles. Recent work from our laboratory identified T cell crossreactivity between epitopes of OspA and lymphocyte function-associated antigen 1␣ L chain (LFA-1␣L) in these patients. We generated a form of rOspA, FTK-OspA, in which the LFA-1␣ L͞rOspA crossreactive T cell epitope was mutated to reduce the possible risk of autoimmunity in genetically susceptible individuals. FTK-OspA did not stimulate human or mouse DR4-restricted, WT-OspA-specific T cells, whereas it did stimulate antibody responses specific for WT-OspA that were similar to mice vaccinated WT-OspA. We show here that the protective efficacy of FTK-OspA is indistinguishable from that of WT-OspA in vaccination trials, as both C3H͞HeJ and BALB͞c FTKOspA-vaccinated mice were protected from Bb infection. These data demonstrate that this rOspA-derived vaccine lacking the predicted cross-reactive T cell epitope, but retaining the capacity to elicit antibodies against infection, is effective in generating protective immunity.

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“…Mice were immunized with 20 µg of DbpA in CFA (Sigma-Aldrich) (day 0) (44). Seven days after immunization, mice were challenged in the hind footpads with 2.5 µg DbpA (50 µl PBS) (44). At the time of immunization, days 2, 4, and 6 after immunization, mice were injected intraperitoneally with 100 µg of native Map extracted from Map + SA, supernatant from Map -SA, or with various concentrations (1-500 µg) of the recombinant proteins Map19, Ace19, or Ace40 in 500 µl of PBS (38,39,41,(46)(47)(48).…”

Section: Methodsmentioning

confidence: 99%

The Staphylococcus aureus Map protein is an immunomodulator that interferes with T cell–mediated responses

Lee¹,

Miyamoto²,

McIntyre³

et al. 2002

J. Clin. Invest.

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Resistance to Lyme disease in decorin-deficient mice

Cited by 127 publications

References 46 publications

Decorin-binding proteins A and B confer distinct mammalian cell type-specific attachment by Borrelia burgdorferi , the Lyme disease spirochete

Decorin-binding proteins A and B confer distinct mammalian cell type-specific attachment by Borrelia burgdorferi , the Lyme disease spirochete

An effective second-generation outer surface protein A-derived Lyme vaccine that eliminates a potentially autoreactive T cell epitope

The Staphylococcus aureus Map protein is an immunomodulator that interferes with T cell–mediated responses

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