Research Article
Laboratory Investigation (2004) 84, 1439–1450, advance online publication, 27 September 2004; doi:10.1038/labinvest.3700177
Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi
Diego Cadavid1,2, Yunhong Bai1,2, Emir Hodzic3, Kavitha Narayan1, Steven W Barthold3 and Andrew R Pachner1
- 1Department of Neurology and Neuroscience, UMDNJ-New Jersey Medical School, Newark, NJ, USA
- 2Center for the Study of Emerging Pathogens, UMDNJ-New Jersey Medical School, Newark, NJ, USA
- 3Center for Comparative Medicine, University of California at Davis, Davis, CA, USA
Correspondence: Dr D Cadavid, MD, Department of Neurology and Neuroscience, UMDNJ-New Jersey Medicine School, 185 South Orange Avenue, MSB H506, Newark, NJ 07103, USA. E-mail: Cadavidi@umdnj.edu
Received 9 March 2004; Revised 13 July 2004; Accepted 16 July 2004; Published online 27 September 2004.
Abstract
To investigate cardiac involvement in the non-human primate (NHP) model of Lyme disease, we inoculated 39 adult Macaca mulatta with Borrelia burgdorferi sensu stricto strains N40 (BbN40) by needle (N=22, 14 immunocompetent (IC), seven permanently immunosuppressed (IS), and four transiently immunosuppressed (TISP)) or by tick-bite (N=4, all TISP) or strain 297 (Bb297) by needle (N=2 IS), or with B. garinii strains Pbi (N=4, 2 TISP and 2 IS), 793 (N=2, TISP) or Pli (N=2, TISP). Five uninfected NHPs were used as controls. Infection and inflammation was studied in the hearts and the aorta removed at necropsy 2–32 months after inoculation by (1) H&E and trichrome-staining; (2) immunohistochemistry and digital image analysis; (3) Western blot densitometry; and (4) TaqMan RT-PCR. All NHPs inoculated with BbN40 became infected and showed carditis at necropsy. The predominant cells were T cells, plasma cells, and macrophages. There was increased IgG and IgM in the heart independent of immunosuppression. The B-cell chemokine BLC was significantly increased in IS-NHPs. There was increased deposition of the complement membrane attack complex (MAC) in TISP and IS-NHPs. The spirochetal load was very high in all BbN40-inoculated IS-NHPs but minimal if any in IC or TISP NHPs. Double-immunostaining revealed that many spirochetes in the heart of BbN40-IS NHPs had MAC on their membranes. We conclude that carditis in NHPs infected with B. burgdorferi is frequent and can persist for years but is mild unless they are immunosupressed.
Keywords:
Borrelia burgdorferi, non-human primates, heart, digital image analysis, plasma cells, BLC, membrane attack complex
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