<i>Borrelia</i>‐Specific Interferon‐γ and Interleukin‐4 Secretion in Cerebrospinal Fluid and Blood during Lyme Borreliosis in Humans: Association with Clinical Outcome

Widhe, Mona; Jarefors, Sara; Ekerfelt, Christina; Vrethem, Magnus; Bergström, Sven; Forsberg, Pia; Ernerudh, Jan

doi:10.1086/382893

Cited by 86 publications

(70 citation statements)

References 46 publications

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“…However, the ratio of these groups of cytokines at different stages of infection appears to be a determining factor in disease outcome. Levels of IFN-␥, IL-4, and IL12p70 produced by B. burgdorferi-stimulated whole blood and PBMCs, or in EM blister fluids, differ between patients with localized or disseminated B. burgdorferi infection (4,(15)(16)(17). Similar observations connecting the nature of the cytokine response with disease outcome have been made using murine models of Lyme borreliosis (18,19).…”

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confidence: 72%

Pattern of Proinflammatory Cytokine Induction in RAW264.7 Mouse Macrophages Is Identical for Virulent and AttenuatedBorrelia burgdorferi

Wang

Petzke

Iyer

et al. 2008

The Journal of Immunology

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Lyme disease pathogenesis results from a complex interaction between Borrelia burgdorferi and the host immune system. The intensity and nature of the inflammatory response of host immune cells to B. burgdorferi may be a determining factor in disease progression. Gene array analysis was used to examine the expression of genes encoding cytokines, chemokines, and related factors in the joint tissue of infected C3H/HeJ mice and in a murine macrophage-like cell line in response to a disseminating or attenuated clinical isolate of B. burgdorferi. Both isolates elicited a robust proinflammatory response in RAW264.7 cells characterized by an increase in transcript levels of genes encoding CC and CXC chemokines, proinflammatory cytokines, and TNF superfamily members. Transcription of genes encoding IL-1β, IL-6, MCP-1, MIP-1α, CXCR4, and TLR2 induced in RAW264.7 cells by either live or heat-killed spirochetes did not differ significantly at any time point over a 24-h period, nor was there a difference in the protein levels of IL-10, TNF-α, IL-6, and IL-12p70 in culture supernatants. Thus, induction of host macrophage expression of proinflammatory mediators by host macrophages does not contribute to the differential pathogenicity of different B. burgdorferi strains.

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confidence: 72%

Pattern of Proinflammatory Cytokine Induction in RAW264.7 Mouse Macrophages Is Identical for Virulent and AttenuatedBorrelia burgdorferi

Wang

Petzke

Iyer

et al. 2008

The Journal of Immunology

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“…A number of peptides (OspA [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] [21,20]. Patients with treatment resistant Lyme arthritis have also been associated with the HLA-DR4, DR2 [27] and DRB1 [28,29], further supporting the involvement of an autoantigen in these patients.…”

Section: Discussionmentioning

confidence: 99%

“…In early experiments a few peptides were more able to stimulate lymphocytes from neuroborreliosis patients, namely no 1 (OspA [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] Blood and CSF cells from patients and controls were stimulated with 29 different high-purity overlapping peptides from OspA ( Table 3). The peptides had a clearcut IFN-c stimulating capacity in lymphocytes from some patients, whereas cells from other patients hardly responded to any of the peptides.…”

Section: Initial Screening Of Peptide Stimulatory Capacitymentioning

confidence: 99%

T‐Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis

et al. 2009

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We studied the T‐cell reactivity to overlapping peptides of B. garinii OspA, in order to locate possible immunodominant T‐cell epitopes in neuroborreliosis. Cells from cerebrospinal fluid (CSF) and blood from 39 patients with neuroborreliosis and 31 controls were stimulated with 31 overlapping peptides, and interferon‐γ secreting cells were detected by ELISPOT. The peptides OspA17–36, OspA49–68, OspA105–124, OspA137–156, OspA193–212 and OspA233–252 showed the highest frequency of positive responses, being positive in CSF from 38% to 50% of patients with neuroborreliosis. These peptides also elicited higher responses in CSF compared with controls (P = 0.004). CSF cells more often showed positive responses to these peptides than blood cells (P = 0.001), in line with a compartmentalization to the central nervous system. Thus, a set of potential T‐cell epitopes were identified in CSF cells from patients with neuroborreliosis. Further studies may reveal whether these epitopes can be used diagnostically and studies involving HLA interactions may show their possible pathogenetic importance.

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“…The presence of IFN-␥, as well as its positive correlation with severity of disease, has been thoroughly documented in human LD (12,13,40,41). However, mice deficient in IFN-␥ or its receptor develop Lyme arthritis that is no less severe than that seen in wild-type animals (42,43).…”

Section: Discussionmentioning

confidence: 99%

IFN-γ Alters the Response ofBorrelia burgdorferi-Activated Endothelium to Favor Chronic Inflammation

Dame

Orenzoff

Palmer

et al. 2007

The Journal of Immunology

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Borrelia burgdorferi, the agent of Lyme disease, promotes proinflammatory changes in the endothelium that lead to the recruitment of leukocytes. The host immune response to infection results in increased levels of IFN-␥ in the serum and lesions of Lyme disease patients that correlate with greater severity of disease. Therefore, the effect of IFN-␥ on the gene expression profile of primary human endothelial cells exposed to B. burgdorferi was determined. B. burgdorferi and IFN-␥ synergistically augmented the expression of 34 genes, 7 of which encode chemokines. Six of these (CCL7, CCL8, CX3CL1, CXCL9, CXCL10, and CXCL11) attract T lymphocytes, and one (CXCL2) is specific for neutrophils. Synergistic production of the attractants for T cells was confirmed at the protein level. IL-1␤, TNF-␣, and LPS also cooperated with IFN-␥ to induce synergistic production of CXCL10 by the endothelium, indicating that IFN-␥ potentiates inflammation in concert with a variety of mediators. An in vitro model of the blood vessel wall revealed that an increased number of human T lymphocytes traversed the endothelium exposed to B. burgdorferi and IFN-␥, as compared with unstimulated endothelial monolayers. In contrast, addition of IFN-␥ diminished the migration of neutrophils across the B. burgdorferi-activated endothelium. IFN-␥ thus alters gene expression by endothelia exposed to B. burgdorferi in a manner that promotes recruitment of T cells and suppresses that of neutrophils. This modulation may facilitate the development of chronic inflammatory lesions in Lyme disease.

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Borrelia‐Specific Interferon‐γ and Interleukin‐4 Secretion in Cerebrospinal Fluid and Blood during Lyme Borreliosis in Humans: Association with Clinical Outcome

Cited by 86 publications

References 46 publications

Pattern of Proinflammatory Cytokine Induction in RAW264.7 Mouse Macrophages Is Identical for Virulent and AttenuatedBorrelia burgdorferi

Pattern of Proinflammatory Cytokine Induction in RAW264.7 Mouse Macrophages Is Identical for Virulent and AttenuatedBorrelia burgdorferi

T‐Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis

IFN-γ Alters the Response ofBorrelia burgdorferi-Activated Endothelium to Favor Chronic Inflammation

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