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Infection and Immunity, July 2003, p. 4003-4010, Vol. 71, No. 7
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.7.4003-4010.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Host-Adapted Borrelia burgdorferi in Mice Expresses OspA during Inflammation
Helena Crowley and Brigitte T. Huber*
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111
Received 14 February 2003/
Returned for modification 21 March 2003/
Accepted 4 April 2003
Antibody responses to outer surface protein A (OspA) of Borrelia burgdorferi may occur during periods of arthritis late in the clinical course of untreated Lyme disease. These antibody responses are paradoxical, given the conclusive evidence demonstrating that B. burgdorferi transmitted to the mammalian host expresses little or no OspA. The parallel occurrence of OspA antibodies and arthritic episodes suggests that OspA expression is upregulated during infection with B. burgdorferi. We hypothesized that this was due to the inflammatory environment caused by the immune response to the spirochete. To test our hypothesis, we adapted an in vivo model that mimics the host-pathogen interaction. Dialysis chambers containing B. burgdorferi were implanted into the peritoneal cavities of mice in the presence or absence of zymosan, a yeast cell wall extract that induces inflammation. Spirochetes were harvested 2 days later, and OspA expression was assessed at the protein and transcription level by Western blotting and real-time reverse transcription-PCR, respectively. Flow cytometry was also utilized to evaluate OspA protein expression on individual spirochetes. B. burgdorferi maintained in an inflammatory in vivo environment show an increased OspA expression relative to B. burgdorferi kept under normal in vivo conditions. Furthermore, host-adapted B. burgdorferi with a low OspA phenotype upregulates OspA expression when transferred to an inflammatory in vivo environment. The results obtained by these techniques uniformly identify inflammation as a mediator of in vivo OspA expression in host-adapted B. burgdorferi, providing insights into the behavior of live spirochetes in the mammalian host.
* Corresponding author. Mailing address: Department of Pathology, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111 Phone: (617) 636-3989 Fax: (617) 636-0449. E-mail: brigitte.huber{at}tufts.edu.
Editor: J. T. Barbieri
Infection and Immunity, July 2003, p. 4003-4010, Vol. 71, No. 7
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.7.4003-4010.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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Copyright © 2003 by the American Society for Microbiology. All rights reserved.