Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi

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 ¼ 22, 14 immunocompetent (IC), seven permanently immunosuppressed (IS), and four transiently immunosuppressed (TISP)) or by tick-bite (N ¼ 4, all TISP) or strain 297 (Bb297) by needle (N ¼ 2 IS), or with B. garinii strains Pbi (N ¼ 4, 2 TISP and 2 IS), 793 (N ¼ 2, TISP) or Pli (N ¼ 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.

Cardiac Apoptosis in Severe Relapsing Fever Borreliosis

“…Borrelia in heart tissue was measured by TaqMan RT-PCR amplification of 16S rRNA using primers and probes common to the genus Borrelia essentially as described previously (6,11). Total RNA was extracted with TRIzole reagent (Life Technologies).…”

“…In previous studies we found severe carditis in nonhuman primates persistently infected with the Lyme disease spirochete Borrelia burgdorferi (11,13) and in antibody-deficient mice (scid) persistently infected with the relapsing fever spirochete Borrelia turicatae (16). Relapsing fever spirochetes are best known for their ability to evade the host's immune response by sequential expression of surface lipoproteins known as variable major proteins, which come in two molecular sizes: variable small proteins (Vsp) and variable large proteins (Vlp) (25).…”

Cardiac manifestations of borreliosis in a dog: a case report

“…It is believed that stabilization of the heart failure prolonged the recovery. No treatment has been shown to reduce or prevent the development of Lyme carditis; however, mild and severe forms are generally treated with oral and intravenous antibiotics, respectively (Cadavid et al, 2004). Furthermore, recent investigations revealed that antibiotic therapy does not eliminate the organism.…”

“…In our patient, corticosteroids were used initially to treat a suspected immune-mediated disease, but were gradually discontinued once Borrelia was confirmed. It is possible that their administration contributed to the patient's deteriorating condition from day 60 to 65 and was connected with ther recurrence of clinical signs after 411 days; corticosteroids can increase the deposition of IgG and IgM in the heart by persistent higher spirochetal load and impaired complement activation that is required for efficient spirochetal elimination (Cadavid et al, 2004).…”

“…The involvement of the heart was first described in dogs by Levy and Durray (1988) in North America; their diagnosis was based on clinical, serological and pathological findings. Interestingly, human and primate B. burgdorferi infections have been associated with cardiomyopathies in Europe, but not in the United States (Cadavid et al, 2004;Bartunek et al, 2007). This case report describes a borrelia serologically-positive Boxer dog, exhibiting heart disease that improved following antibiotic treatment and cardiac support.…”