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Infection and Immunity, November 2005, p. 7669-7676, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7669-7676.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Cardiac Apoptosis in Severe Relapsing Fever Borreliosis

Diana Londoño,1 Yunhong Bai,1 Wolfram R. Zückert,2 Harald Gelderblom,1 and Diego Cadavid1*

Department of Neurology and Neuroscience and Center for the Study of Emerging Pathogens, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey,1 Department of Microbiology, Molecular Genetics and Immunology, The University of Kansas Medical Center, Kansas City, Kansas2

Received 13 June 2005/ Returned for modification 14 July 2005/ Accepted 18 August 2005

Previous studies revealed that the heart suffers significant injury during experimental Lyme and relapsing fever borreliosis when the immune response is impaired (D. Cadavid, Y. Bai, E. Hodzic, K. Narayan, S. W. Barthold, and A. R. Pachner, Lab. Investig. 84:1439-1450, 2004; D. Cadavid, T. O'Neill, H. Schaefer, and A. R. Pachner, Lab. Investig. 80:1043-1054, 2000; and D. Cadavid, D. D. Thomas, R. Crawley, and A. G. Barbour, J. Exp. Med. 179:631-642, 1994). To investigate cardiac injury in borrelia carditis, we used antibody-deficient mice persistently infected with isogenic serotypes of the relapsing fever agent Borrelia turicatae. We studied infection in hearts 1 to 2 months after inoculation by TaqMan reverse transcription-PCR and immunohistochemistry (IHC) and inflammation by hematoxylin and eosin and trichrome staining, IHC, and in situ hybridization (ISH). We studied apoptosis by terminal transferase-mediated DNA nick end labeling assay and measured expression of apoptotic molecules by RNase protection assay, immunofluorescence, and immunoblot. All antibody-deficient mice, but none of the immunocompetent controls, developed persistent infection of the heart. Antibody-deficient mice infected with serotype 2 had more severe cardiac infection and injury than serotype 1-infected mice. The injury was more severe around the base of the heart and pericardium, corresponding to sites of marked infiltration by activated macrophages and upregulation of interleukin-6 (IL-6). Infected hearts showed evidence of apoptosis of macrophages and cardiomyocytes as well as significant upregulation of caspases, most notably caspase-1. We conclude that persistent infection with relapsing fever borrelias causes significant loss of cardiomyocytes associated with prominent infiltration by activated macrophages, upregulation of IL-6, induction of caspase-1, and apoptosis.

* Corresponding author. Mailing address: Department of Neurology and Neuroscience and Center for the Study of Emerging Pathogens, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, MSB H506, Newark, NJ 07103. Phone: (973) 972-8686. Fax: (973) 972-5059. E-mail: cadavidi{at}umdnj.edu.

Editor: D. L. Burns

Infection and Immunity, November 2005, p. 7669-7676, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7669-7676.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Londono, D., Marques, A., Hornung, R. L., Cadavid, D. (2008). Relapsing Fever Borreliosis in Interleukin-10-Deficient Mice. Infect. Immun. 76: 5508-5513 [Abstract] [Full Text]  
  • Londono, D., Marques, A., Hornung, R. L., Cadavid, D. (2008). IL-10 Helps Control Pathogen Load during High-Level Bacteremia. J. Immunol. 181: 2076-2083 [Abstract] [Full Text]  
  • Gelderblom, H., Schmidt, J., Londono, D., Bai, Y., Quandt, J., Hornung, R., Marques, A., Martin, R., Cadavid, D. (2007). Role of Interleukin 10 during Persistent Infection with the Relapsing Fever Spirochete Borrelia turicatae. Am. J. Pathol. 170: 251-262 [Abstract] [Full Text]  
  • Lawson, C. L., Yung, B. H., Barbour, A. G., Zuckert, W. R. (2006). Crystal Structure of Neurotropism-Associated Variable Surface Protein 1 (Vsp1) of Borrelia turicatae.. J. Bacteriol. 188: 4522-4530 [Abstract] [Full Text]  


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