Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 179K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Liang, F. T. Articles by Philipp, M. T. Search for Related Content PubMed PubMed Citation Articles by Liang, F. T. Articles by Philipp, M. T. Pubmed/NCBI databases Medline Plus Health Information Lyme Disease Social Bookmarking                            What's this?

Original Article

Department of Parasitology, Tulane Regional Primate Research Center, Tulane University Health Sciences Center, Covington, LA 70433

Address correspondence to Mario T. Philipp, Tulane Regional Primate Research Center, Tulane University Health Sciences Center, 18703 Three Rivers Rd., Covington, LA 70433. Phone: 985-871-6221; Fax: 985-871-6390; E-mail: philipp{at}tpc.tulane.edu

Borrelia burgdorferi, the Lyme disease spirochete, persistently infects mammalian hosts despite the development of strong humoral responses directed against the pathogen. Here we describe a novel mechanism of immune evasion by B. burgdorferi. In immunocompetent mice, spirochetes that did not express ospC (the outer-surface protein C gene) were selected within 17 d after inoculation, concomitantly with the emergence of anti-OspC antibody. Spirochetes with no detectable OspC transcript that were isolated from immunocompetent mice reexpressed ospC after they were either cultured in vitro or transplanted to naive immunocompetent mice, but not in OspC-immunized mice. B. burgdorferi persistently expressed ospC in severe combined immune-deficient (SCID) mice. Passive immunization of B. burgdorferi–infected SCID mice with an anti-OspC monoclonal antibody selectively eliminated ospC-expressing spirochetes but did not clear the infection. OspC-expressing spirochetes reappeared in SCID mice after the anti-OspC antibody was eliminated. We submit that selection of surface-antigen nonexpressers is an immune evasion mechanism that contributes to spirochetal persistence.

Key Words: Borrelia burgdorferi • OspC • chronic infection • immune evasion • immune selection

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Tilly, K., Bestor, A., Dulebohn, D. P., Rosa, P. A. (2009). OspC-Independent Infection and Dissemination by Host-Adapted Borrelia burgdorferi. Infect. Immun. 77: 2672-2682 [Abstract] [Full Text]  
• Brissette, C. A., Haupt, K., Barthel, D., Cooley, A. E., Bowman, A., Skerka, C., Wallich, R., Zipfel, P. F., Kraiczy, P., Stevenson, B. (2009). Borrelia burgdorferi Infection-Associated Surface Proteins ErpP, ErpA, and ErpC Bind Human Plasminogen. Infect. Immun. 77: 300-306 [Abstract] [Full Text]  
• Malkiel, S., Kuhlow, C. J., Mena, P., Benach, J. L. (2009). The Loss and Gain of Marginal Zone and Peritoneal B Cells Is Different in Response to Relapsing Fever and Lyme Disease Borrelia. J. Immunol. 182: 498-506 [Abstract] [Full Text]  
• Xu, Q., McShan, K., Liang, F. T. (2008). Modification of Borrelia burgdorferi to overproduce OspA or VlsE alters its infectious behaviour. Microbiology 154: 3420-3429 [Abstract] [Full Text]  
• Embers, M. E., Alvarez, X., Ooms, T., Philipp, M. T. (2008). The Failure of Immune Response Evasion by Linear Plasmid 28-1-Deficient Borrelia burgdorferi Is Attributable to Persistent Expression of an Outer Surface Protein. Infect. Immun. 76: 3984-3991 [Abstract] [Full Text]  
• Livengood, J. A., Schmit, V. L., Gilmore, R. D. Jr. (2008). Global Transcriptome Analysis of Borrelia burgdorferi during Association with Human Neuroglial Cells. Infect. Immun. 76: 298-307 [Abstract] [Full Text]  
• Bykowski, T., Woodman, M. E., Cooley, A. E., Brissette, C. A., Brade, V., Wallich, R., Kraiczy, P., Stevenson, B. (2007). Coordinated Expression of Borrelia burgdorferi Complement Regulator-Acquiring Surface Proteins during the Lyme Disease Spirochete's Mammal-Tick Infection Cycle. Infect. Immun. 75: 4227-4236 [Abstract] [Full Text]  
• Xu, Q., Seemanaplli, S. V., McShan, K., Liang, F. T. (2007). Increasing the Interaction of Borrelia burgdorferi with Decorin Significantly Reduces the 50 Percent Infectious Dose and Severely Impairs Dissemination. Infect. Immun. 75: 4272-4281 [Abstract] [Full Text]  
• Hermann, C. (2007). Review: Variability of host pathogen interaction. Innate Immunity 13: 199-218 [Abstract]  
• Gilmore, R. D. Jr., Howison, R. R., Schmit, V. L., Nowalk, A. J., Clifton, D. R., Nolder, C., Hughes, J. L., Carroll, J. A. (2007). Temporal Expression Analysis of the Borrelia burgdorferi Paralogous Gene Family 54 Genes BBA64, BBA65, and BBA66 during Persistent Infection in Mice. Infect. Immun. 75: 2753-2764 [Abstract] [Full Text]  
• Tilly, K., Bestor, A., Jewett, M. W., Rosa, P. (2007). Rapid Clearance of Lyme Disease Spirochetes Lacking OspC from Skin. Infect. Immun. 75: 1517-1519 [Abstract] [Full Text]  
• Mueller, M., Bunk, S., Diterich, I., Weichel, M., Rauter, C., Hassler, D., Hermann, C., Crameri, R., Hartung, T. (2006). Identification of Borrelia burgdorferi Ribosomal Protein L25 by the Phage Surface Display Method and Evaluation of the Protein's Value for Serodiagnosis.. J. Clin. Microbiol. 44: 3778-3780 [Abstract] [Full Text]  
• Xu, Q., Seemanapalli, S. V., McShan, K., Liang, F. T. (2006). Constitutive Expression of Outer Surface Protein C Diminishes the Ability of Borrelia burgdorferi To Evade Specific Humoral Immunity. Infect. Immun. 74: 5177-5184 [Abstract] [Full Text]  
• Stewart, P. E., Wang, X., Bueschel, D. M., Clifton, D. R., Grimm, D., Tilly, K., Carroll, J. A., Weis, J. J., Rosa, P. A. (2006). Delineating the Requirement for the Borrelia burgdorferi Virulence Factor OspC in the Mammalian Host.. Infect. Immun. 74: 3547-3553 [Abstract] [Full Text]  
• Tilly, K., Krum, J. G., Bestor, A., Jewett, M. W., Grimm, D., Bueschel, D., Byram, R., Dorward, D., VanRaden, M. J., Stewart, P., Rosa, P. (2006). Borrelia burgdorferi OspC Protein Required Exclusively in a Crucial Early Stage of Mammalian Infection.. Infect. Immun. 74: 3554-3564 [Abstract] [Full Text]  
• Xu, Q., Seemanapalli, S. V., Lomax, L., McShan, K., Li, X., Fikrig, E., Liang, F. T. (2005). Association of Linear Plasmid 28-1 with an Arthritic Phenotype of Borrelia burgdorferi. Infect. Immun. 73: 7208-7215 [Abstract] [Full Text]  
• von Lackum, K., Miller, J. C., Bykowski, T., Riley, S. P., Woodman, M. E., Brade, V., Kraiczy, P., Stevenson, B., Wallich, R. (2005). Borrelia burgdorferi Regulates Expression of Complement Regulator-Acquiring Surface Protein 1 during the Mammal-Tick Infection Cycle. Infect. Immun. 73: 7398-7405 [Abstract] [Full Text]  
• Porcella, S. F., Raffel, S. J., Anderson, D. E. Jr., Gilk, S. D., Bono, J. L., Schrumpf, M. E., Schwan, T. G. (2005). Variable Tick Protein in Two Genomic Groups of the Relapsing Fever Spirochete Borrelia hermsii in Western North America. Infect. Immun. 73: 6647-6658 [Abstract] [Full Text]  
• Ojaimi, C., Mulay, V., Liveris, D., Iyer, R., Schwartz, I. (2005). Comparative Transcriptional Profiling of Borrelia burgdorferi Clinical Isolates Differing in Capacities for Hematogenous Dissemination. Infect. Immun. 73: 6791-6802 [Abstract] [Full Text]  
• Salazar, J. C., Pope, C. D., Moore, M. W., Pope, J., Kiely, T. G., Radolf, J. D. (2005). Lipoprotein-Dependent and -Independent Immune Responses to Spirochetal Infection. CVI 12: 949-958 [Abstract] [Full Text]  
• Salazar, C. A., Rothemich, M., Drouin, E. E., Glickstein, L., Steere, A. C. (2005). Human Lyme Arthritis and the Immunoglobulin G Antibody Response to the 37-Kilodalton Arthritis-Related Protein of Borrelia burgdorferi. Infect. Immun. 73: 2951-2957 [Abstract] [Full Text]  
• Zhang, H., Raji, A., Theisen, M., Hansen, P. R., Marconi, R. T. (2005). bdrF2 of Lyme Disease Spirochetes Is Coexpressed with a Series of Cytoplasmic Proteins and Is Produced Specifically during Early Infection. J. Bacteriol. 187: 175-184 [Abstract] [Full Text]  
• Liang, F. T., Yan, J., Mbow, M. L., Sviat, S. L., Gilmore, R. D., Mamula, M., Fikrig, E. (2004). Borrelia burgdorferi Changes Its Surface Antigenic Expression in Response to Host Immune Responses. Infect. Immun. 72: 5759-5767 [Abstract] [Full Text]  
• Crother, T. R., Champion, C. I., Whitelegge, J. P., Aguilera, R., Wu, X.-Y., Blanco, D. R., Miller, J. N., Lovett, M. A. (2004). Temporal Analysis of the Antigenic Composition of Borrelia burgdorferi during Infection in Rabbit Skin. Infect. Immun. 72: 5063-5072 [Abstract] [Full Text]  
• Liang, F. T., Brown, E. L., Wang, T., Iozzo, R. V., Fikrig, E. (2004). Protective Niche for Borrelia burgdorferi to Evade Humoral Immunity. Am. J. Pathol. 165: 977-985 [Abstract] [Full Text]  
• Liu, N., Montgomery, R. R., Barthold, S. W., Bockenstedt, L. K. (2004). Myeloid Differentiation Antigen 88 Deficiency Impairs Pathogen Clearance but Does Not Alter Inflammation in Borrelia burgdorferi-Infected Mice. Infect. Immun. 72: 3195-3203 [Abstract] [Full Text]  
• Grimm, D., Tilly, K., Byram, R., Stewart, P. E., Krum, J. G., Bueschel, D. M., Schwan, T. G., Policastro, P. F., Elias, A. F., Rosa, P. A. (2004). Outer-surface protein C of the Lyme disease spirochete: A protein induced in ticks for infection of mammals. Proc. Natl. Acad. Sci. USA 101: 3142-3147 [Abstract] [Full Text]  
• Seshu, J., Boylan, J. A., Gherardini, F. C., Skare, J. T. (2004). Dissolved Oxygen Levels Alter Gene Expression and Antigen Profiles in Borrelia burgdorferi. Infect. Immun. 72: 1580-1586 [Abstract] [Full Text]  
• Kraiczy, P., Hellwage, J., Skerka, C., Becker, H., Kirschfink, M., Simon, M. M., Brade, V., Zipfel, P. F., Wallich, R. (2004). Complement Resistance of Borrelia burgdorferi Correlates with the Expression of BbCRASP-1, a Novel Linear Plasmid-encoded Surface Protein That Interacts with Human Factor H and FHL-1 and Is Unrelated to Erp Proteins. J. Biol. Chem. 279: 2421-2429 [Abstract] [Full Text]  
• Narasimhan, S., Caimano, M. J., Liang, F. T., Santiago, F., Laskowski, M., Philipp, M. T., Pachner, A. R., Radolf, J. D., Fikrig, E. (2003). Borrelia burgdorferi transcriptome in the central nervous system of non-human primates. Proc. Natl. Acad. Sci. USA 100: 15953-15958 [Abstract] [Full Text]  
• Labandeira-Rey, M., Seshu, J., Skare, J. T. (2003). The Absence of Linear Plasmid 25 or 28-1 of Borrelia burgdorferi Dramatically Alters the Kinetics of Experimental Infection via Distinct Mechanisms. Infect. Immun. 71: 4608-4613 [Abstract] [Full Text]  
• Gilmore, R. D. Jr, Bacon, R. M., Carpio, A. M., Piesman, J., Dolan, M. C., Mbow, M. L. (2003). Inability of outer-surface protein C (OspC)-primed mice to elicit a protective anamnestic immune response to a tick-transmitted challenge of Borrelia burgdorferi. J Med Microbiol 52: 551-556 [Abstract] [Full Text]  
• Crother, T. R., Champion, C. I., Wu, X.-Y., Blanco, D. R., Miller, J. N., Lovett, M. A. (2003). Antigenic Composition of Borrelia burgdorferi during Infection of SCID Mice. Infect. Immun. 71: 3419-3428 [Abstract] [Full Text]  
• McDowell, J. V., Wolfgang, J., Tran, E., Metts, M. S., Hamilton, D., Marconi, R. T. (2003). Comprehensive Analysis of the Factor H Binding Capabilities of Borrelia Species Associated with Lyme Disease: Delineation of Two Distinct Classes of Factor H Binding Proteins. Infect. Immun. 71: 3597-3602 [Abstract] [Full Text]  
• Liang, F. T., Nelson, F. K., Fikrig, E. (2002). Molecular Adaptation of Borrelia burgdorferi in the Murine Host. JEM 196: 275-280 [Abstract] [Full Text]  
• Hefty, P. S., Jolliff, S. E., Caimano, M. J., Wikel, S. K., Akins, D. R. (2002). Changes in Temporal and Spatial Patterns of Outer Surface Lipoprotein Expression Generate Population Heterogeneity and Antigenic Diversity in the Lyme Disease Spirochete, Borrelia burgdorferi. Infect. Immun. 70: 3468-3478 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS