Increased Expression of B-Lymphocyte Chemoattractant, but Not Pro-Inflammatory Cytokines, in Muscle Tissue in Rhesus Chronic Lyme Borreliosis

Pachner, Andrew R.; Dail, Donna; Narayan, Kavitha; Dutta, Kaberi; Cadavid, Diego

doi:10.1006/cyto.2002.1973

Cited by 29 publications

(23 citation statements)

References 54 publications

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“…25 In a previous study, we found significantly increased levels of BLC mRNA in skeletal muscle from TISPNHPs inoculated with BbN40 compared with controls that were uninfected or inoculated but not infected. 26 As expected, a dramatic effect of the immunosuppression was an inability to fight the infection. One reason why IS-NHPs failed to control the infection was the lower levels of circulating specific antibody, as previously reported.…”

Section: Discussionmentioning

confidence: 55%

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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Section: Discussionmentioning

confidence: 55%

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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“…Similar to the heart, inflammation in skeletal muscle and spinal cord was associated with infiltration by T and plasma cells, deposition of antibody and complement, and upregulation of CXCL13 [14]. Indeed, RT-PCR confirmed that CXCL13 was the only one of many cytokines or chemokines examined that was significantly upregulated in muscles with B. burgdorferi myositis [18]. More recent data showed a strong positive correlation between BLC mRNA and spirochetal infection across all tissues [14].…”

Section: Tissue Response To B Burgdorferi Infection In Non-human Primentioning

confidence: 84%

“…For this we did microscopical examination of H&E-and immunostained tissue sections and measured mRNA and protein by RT-PCR and immuno-dot-blot, respectively [1,4,5,8,[14][15][16]18]. First we studied the presence and severity of inflammation in tissues from immunocompetent and immunosuppressed non-human primates inoculated with the N40 strain of B. burgdorferi [8].…”

Section: Tissue Response To B Burgdorferi Infection In Non-human Primentioning

confidence: 99%

The mammalian host response to borrelia infection

Cadavid

2006

Wien Klin Wochenschr

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Tick-borne relapsing fever (RF) and Lyme disease (LD) are spirochetal infections of humans caused by different Borrelia species in endemic areas throughout the world. Our laboratory is studying the response of mammalian hosts to borrelia infection in RF and LD. For this, we use mice and non-human primates infected with B. burgdorferi sensu stricto strain N40 (N40) and the Oz1 strain of Borrelia turicatae (Bt), agents of LD and RF in North America, respectively. Our results have revealed that outbred non-human primates are significantly less susceptible than outbred mice to persistent infection with N40. In contrast, the majority of mice inoculated with the RF agent B. turicatae clear the infection, with the notable exception of residual brain or blood infection in up to 25% of cases. Little if any tissue injury occurs in immunocompetent animals with either LD or RF. In contrast, impairment of specific antibody production results in significant tissue injury, most notably in the heart, in both LD and RF. The inflammatory infiltrate is rich in plasma cells, activated macrophages and T cells, and there is significant deposition of antibody and complement, including membrane attack complex, in inflamed tissues and spirochetes. Significant loss of cardiomyocytes with apoptosis and caspase activation was observed in the heart of immunosuppressed non-human primates infected with N40 and in B cell-deficient mice infected with B. turicatae. Unlike the heart, the brain of B cell-deficient mice infected with B. turicatae showed prominent microglial activation but no detectable tissue injury. Tissues from immunosuppressed non-human primates infected with N40 produce large amounts of immunoglobulin and the B cell chemokine CXCL13, both of which significantly correlate with the spirochetal load. We conclude that the main response of mammalian hosts in LD and RF is the production of specific antibody to clear the infection. Failure of this response leads to persistent infection, which can lead to tissue injury, most notably in the heart.

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“…Thus, the data demonstrate that the B. burgdorferi infectioninduced destruction of the lymph node architecture precedes the accumulation of CD19 ϩ B cells at that site. production (15,21,22). Therefore, we investigated to what extent changes in CXCL13 or the other major known lymph node-homing chemokines might underlie these infection-induced lymph node changes.…”

Section: Resultsmentioning

confidence: 99%

MyD88- and TRIF-Independent Induction of Type I Interferon Drives Naive B Cell Accumulation but Not Loss of Lymph Node Architecture in Lyme Disease

et al. 2014

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Rapidly after infection, live Borrelia burgdorferi, the causative agent of Lyme disease, is found within lymph nodes, causing rapid and strong tissue enlargement, a loss of demarcation between B cell follicles and T cell zones, and an unusually large accumulation of B cells. We sought to explore the mechanisms underlying these changes, as lymph tissue disruption could be detrimental for the development of robust Borrelia-specific immunity. A time course study demonstrated that the loss of the normal lymph node structure was a distinct process that preceded the strong increases in B cells at the site. The selective increases in B cell frequencies were due not to proliferation but rather to cytokine-mediated repositioning of B cells to the lymph nodes, as shown with various gene-targeted and bone marrow irradiation chimeras. These studies demonstrated that B. burgdorferi infection induced type I interferon receptor (IFNR) signaling in lymph nodes in a MyD88-and TRIF-independent manner and that type I IFNR indirect signaling was required for the excessive increases of naive B cells at those sites. It did not, however, drive the observed histopathological changes, which occurred independently also from major shifts in the lymphocyte-homing chemokines, CXCL12, CXCL13, and CCL19/21, as shown by quantitative reverse transcription-PCR (qRT-PCR), flow cytometry, and transwell migration experiments. Thus, B. burgdorferi infection drives the production of type I IFN in lymph nodes and in so doing strongly alters the cellular composition of the lymph nodes, with potential detrimental effects for the development of robust Borrelia-specific immunity.

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Increased Expression of B-Lymphocyte Chemoattractant, but Not Pro-Inflammatory Cytokines, in Muscle Tissue in Rhesus Chronic Lyme Borreliosis

Cited by 29 publications

References 54 publications

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

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

The mammalian host response to borrelia infection

MyD88- and TRIF-Independent Induction of Type I Interferon Drives Naive B Cell Accumulation but Not Loss of Lymph Node Architecture in Lyme Disease

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