ArticleJournal of neuroinflammation2015
Inflammatory mediator release from primary rhesus microglia in response to Borrelia burgdorferi results from the activation of several receptors and pathways.
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- The FGF/FGFR system in the microglial neuroinflammation with Borrelia burgdorferi: likely intersectionality with other neurological conditions.Journal of neuroinflammation · 2023Article
- Neuropathogenicity of non-viable Borrelia burgdorferi ex vivo.Scientific reports · 2022Article
- Pathogenesis of Borrelia burgdorferi and Babesia microti in TLR4-Competent and TLR4-dysfunctional C3H mice.Cellular microbiology · 2021Article
- Immune Response toCurrent issues in molecular biology · 2021Article
- Lyme Neuroborreliosis: Clinical Outcomes, Controversy, Pathogenesis, and Polymicrobial Infections.Annals of neurology · 2019Review
- Intracellular TLR7 is activated in human oligodendrocytes in response to Borrelia burgdorferi exposure.Neuroscience letters · 2018Article
- Primary Human Microglia Are Phagocytically Active and Respond toFrontiers in microbiology · 2018Article
- Receptor tyrosine kinases play a significant role in human oligodendrocyte inflammation and cell death associated with the Lyme disease bacterium Borrelia burgdorferi.Journal of neuroinflammation · 2017Article
- Matrix metalloproteinase activity stimulates N-cadherin shedding and the soluble N-cadherin ectodomain promotes classical microglial activation.Journal of neuroinflammation · 2017Article
- Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system.Journal of neuroinflammation · 2017Article
- MicroRNA and mRNA Transcriptome Profiling in Primary Human Astrocytes Infected with Borrelia burgdorferi.PloS one · 2017Article
- Toll-Like Receptor 1/2 and 5 Ligands Enhance the Expression of Cyclin D1 and D3 and Induce Proliferation in Mantle Cell Lymphoma.PloS one · 2016Article
- Antagonist of the neurokinin-1 receptor curbs neuroinflammation in ex vivo and in vitro models of Lyme neuroborreliosis.Journal of neuroinflammation · 2015Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIn previous studies, neurons were documented to undergo apoptosis in the presence of microglia and live Borrelia burgdorferi, but not with either agent alone. Microscopy showed that several Toll-like receptors (TLRs) were upregulated in microglia upon B. burgdorferi exposure. It was hypothesized that the inflammatory milieu generated by microglia in the presence of B. burgdorferi results in neuronal apoptosis and that this inflammation was likely generated through TLR pathways.
methodsIn this study, we explored the role of several TLR and nucleotide-binding oligomerization domain containing 2 (NOD2)-dependent pathways in inducing inflammation in the presence of B. burgdorferi, using ribonucleic acid interference (RNAi) and/or inhibitors, in primary non-human primate (NHP) microglia. We also used several inhibitors for key mitogen-activated protein kinase (MAPK) pathways to determine the role of downstream pathways in inflammatory mediator release.
resultsThe results show that the TLR2 pathway plays a predominant role in inducing inflammation, as inhibition of TLR2 with either small interfering RNA (siRNA) or inhibitor, in the presence of B. burgdorferi, significantly downregulated interleukin 6 (IL-6), chemokine (C-X-C) motif ligand 8 (CXCL8), chemokine (C-C) motif ligand 2 (CCL2), and tumor necrosis factor (TNF) production. This was followed by TLR5, the silencing of which significantly downregulated IL-6 and TNF. The role of TLR4 was inconclusive as a TLR4-specific inhibitor and TLR4 siRNA had opposing effects in the presence of B. burgdorferi. Silencing of NOD2 by siRNA in the presence of B. burgdorferi significantly upregulated IL-6, CCL2, and TNF. Downstream signaling involved the adaptor molecule myeloid differentiation primary response 88 (MyD88), as expected, as well as the MAPK pathways, with extracellular signal-regulated kinase (ERK) being predominant, followed by Jun N-terminal kinase (JNK) and p38 pathways.
conclusionsSeveral receptors and pathways, with both positive and negative effects, mediate inflammation of primary microglia in response to B. burgdorferi, resulting in a complex, tightly regulated immune network.
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