Central and peripheral nervous system infection, immunity, and inflammation in the nonhuman primate model of lyme borreliosis

Pachner, Andrew R.; Cadavid, Diego; Shu, Gale; Dail, Donna; Pachner, Sarah; Hodzic, Emir; Barthold, Stephen W.

doi:10.1002/ana.1287.abs

Cited by 14 publications

(35 citation statements)

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“…During infections of immunosuppressed NHPs inoculated by syringe with N40, we found that skeletal muscles had the highest spirochetal load of all the tissues examined (11). During infections of transiently immunosuppressed (TISP) NHPs, we found that skeletal and cardiac muscles had the most severe inflammation of all the tissues examined (40).…”

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confidence: 81%

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Infection and Inflammation in Skeletal Muscle fromNonhuman Primates Infected with Different Genospecies of theLyme Disease SpirocheteBorreliaburgdorferi

et al. 2003

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Lyme borreliosis is a multisystemic disease caused by various genospecies of the spirochete Borrelia burgdorferi. To investigate muscle involvement in the nonhuman primate (NHP) model of Lyme disease, 16 adult Macaca mulatta animals inoculated with strain N40 of B. burgdorferi sensu strictu by syringe or by tick bite or with strain Pbi of B. burgdorferi genospecies garinii by syringe were studied. Animals were necropsied while immunosuppressed on day 50 (two animals each inoculated with B. burgdorferi N40 by syringe and with B. garinii Pbi by syringe) or on day 90, 40 days after immunosuppression had been discontinued (four animals each inoculated with strain N40 by syringe, with strain N40 by tick bite, and with strain Pbi by syringe). Skeletal muscles removed at necropsy were studied by (i) microscopic examination of hematoxylin-eosinstained sections for inflammation and tissue injury; (ii) immunohistochemical and digital image analyses for antibody and complement deposition and cellular inflammation; (iii) Western blot densitometry for the presence of antibodies; and (iv) reverse transcription-PCR for measurement of the spirochetal load or C1q (the first component of the complement cascade) synthesis. The results showed that N40 was more infectious for NHPs than Pbi. NHPs inoculated with N40 but not with Pbi developed myositis. The inflammation in skeletal muscle was more severe in NHPs inoculated with N40 by syringe than in those inoculated by tick bite. The predominant cells in the inflammatory infiltrate were T cells and plasma cells. The deposition of antibody and complement in inflamed muscles from N40-inoculated NHPs was significantly higher than that in Pbiinoculated NHPs. The spirochetal load was very high in the two N40-inoculated NHPs examined while they were immunosuppressed but decreased to minimal levels in the NHPs when immunocompetence was restored. We conclude that myositis can be a prominent feature of Lyme borreliosis depending on the infecting organism and host immune status.

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confidence: 81%

“…strains were used for inoculation. B. burgdorferi sensu stricto strain N40 was used in previous studies with the NHP model of Lyme disease (40)(41)(42). For the first time, some NHPs were inoculated with strain N40 by tick bite rather than by needle.…”

Section: Methodsmentioning

confidence: 99%

Infection and Inflammation in Skeletal Muscle fromNonhuman Primates Infected with Different Genospecies of theLyme Disease SpirocheteBorreliaburgdorferi

et al. 2003

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“…5 The immunoblot for all inoculated NHPs have been reported. 5,16,17 Table 1 also summarizes the immunoblot results for the BbN40-inoculated immunocompetent NHPs: all that were tested had positive Lyme IgG WB at necropsy and none had positive IgM WB when examined later than 6 months after inoculation. All WB from garinii-inoculated NHPs were negative even when tested with homologous sonicates, 5 an indication that NHPs are resistant to syringe inoculation of garinii strains of Lyme disease borrelias.…”

Section: Antibody Responsementioning

confidence: 99%

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

Cadavid

Bai

Hodzic

et al. 2004

Laboratory Investigation

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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.

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“…Commercial B. burgdorferi sensu stricto nitrocellulose strips (Microbiology Reference Laboratory, Cypress, CA, USA) were used as previously described 10,14 according to the instructions of the diagnostic kit. The strain used for preparation of these blots was a B. burgdorferi sensu stricto strain CB, an isolate from an erythema migrans lesion from a patient from Valhalla, NY.…”

Section: Immunoblottingmentioning

confidence: 99%

“…13 Both inflammation and infection are more prominent in the periphery than in the CNS. 13,14 The preferred localization in the spinal cord were the leptomeninges, nerve roots, and dorsal root ganglia. 13 For the present study, we focused on the spinal cord.…”

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Spinal cord involvement in the nonhuman primate model of Lyme disease

Bai

Narayan

Dail

et al. 2004

Laboratory Investigation

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Lyme borreliosis is a multisystemic disease caused by infection with various genospecies of the spirochete Borrelia burgdorferi. The organs most often affected are the skin, joints, the heart, and the central and peripheral nervous systems. Multiple neurological complications can occur, including aseptic meningitis, encephalopathy, facial nerve palsy, radiculitis, myelitis, and peripheral neuropathy. To investigate spinal cord involvement in the nonhuman primate (NHP) model of Lyme borreliosis, we inoculated 25 adult Macaca mulatta with B. burgdorferi sensu strictu strains N40 by needle (N ¼ 9) or by tick (N ¼ 4) or 297 by needle (N ¼ 2), or with B. burgdorferi genospecies garinii strains Pbi (N ¼ 4), 793 (N ¼ 2), or Pli (N ¼ 4) by needle. Immunosuppression either transiently (TISP) or permanently (IS) was used to facilitate establishment of infection. Tissues and fluids were collected at necropsy 7-24 weeks later. Hematoxylin and eosin staining was used to study inflammation, and immunohistochemistry and digital image analysis to measure inflammation and localize spirochetes. The spirochetal load and C1q expression were measured by TaqMan RT-PCR. The results showed meningoradiculitis developed in only one of the 25 NHP's examined, TISP NHP 321 inoculated with B. garinii strain Pbi. Inflammation was localized to nerve roots, dorsal root ganglia, and leptomeninges but rarely to the spinal cord parenchyma itself. T cells and plasma cells were the predominant inflammatory cells. Significantly increased amounts of IgG, IgM, and C1q were found in inflamed spinal cord. Taqman RT-PCR found spirochetes in the spinal cord only in IS-NHP's, mostly in nerve roots and ganglia rather than in the cord parenchyma. C1q mRNA expression was significantly increased in inflamed spinal cord. This is the first comprehensive study of spinal cord involvement in Lyme borreliosis.

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Central and peripheral nervous system infection, immunity, and inflammation in the nonhuman primate model of lyme borreliosis

Cited by 14 publications

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Infection and Inflammation in Skeletal Muscle fromNonhuman Primates Infected with Different Genospecies of theLyme Disease SpirocheteBorreliaburgdorferi

Infection and Inflammation in Skeletal Muscle fromNonhuman Primates Infected with Different Genospecies of theLyme Disease SpirocheteBorreliaburgdorferi

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

Spinal cord involvement in the nonhuman primate model of Lyme disease

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