ArticleProceedings of the National Academy of Sciences of the United States of America2011
Phagosomal signaling by Borrelia burgdorferi in human monocytes involves Toll-like receptor (TLR) 2 and TLR8 cooperativity and TLR8-mediated induction of IFN-beta.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
81 citing papers in PubMed, 143 citations in OpenAlex.
- Induction of indoleamine 2,3-dioxygenase by Borrelia burgdorferi in human immune cells correlates with pathogenic potential.Journal of leukocyte biology · 2015Trial
- Human TLR8 is activated upon recognition of Borrelia burgdorferi RNA in the phagosome of human monocytes.Journal of leukocyte biology · 2013Trial
- Mostly getting along -Borrelia burgdorferi and its manipulation of the host immune system.ImmunoHorizons · 2026Review
- Developing a durable, memory-driven, CspZ-targeting Lyme disease vaccine by rational adjuvant selection.NPJ vaccines · 2026Article
- Borrelia burgdorferi sensu lato Employs Several Escape Mechanisms to Bypass the Human Defense System.European journal of immunology · 2026Review
- Lyme borreliosis.Nature reviews. Disease primers · 2026Review
- Type I interferon signaling promotes early innate control ofbioRxiv : the preprint server for biology · 2026Article
- Develop a durable, memory-driven, CspZ-targeting Lyme disease vaccine by rationale adjuvant selection.bioRxiv : the preprint server for biology · 2026Article
- Characterizing the impact of intracutaneous dissemination on host responses duringFrontiers in immunology · 2026Article
- Role of dual specificity phosphatase 1 in influencing inflammatory pathways in macrophages modulated byFrontiers in immunology · 2026Article
- Role of Dual Specificity Phosphatase 1 (DUSP1) in influencing inflammatory pathways in macrophages modulated bybioRxiv : the preprint server for biology · 2025Article
- Phagosomal RNA sensing through TLR8 controls susceptibility to tuberculosis.Cell reports · 2025Article
- Toll-like receptor 1 polymorphism is associated with impaired immune tolerance, dysregulated inflammatory responses toFrontiers in immunology · 2025Article
- miR-574-5p in epigenetic regulation and Toll-like receptor signaling.Cell communication and signaling : CCS · 2024Review
- Bacterial RNA sensing by TLR8 requires RNase 6 processing and is inhibited by RNA 2'O-methylation.EMBO reports · 2024Article
- Changes in the Transcriptome and Long Non-Coding RNAs but Not the Methylome Occur in Human Cells Exposed toGenes · 2024Article
- Borrelia burgdorferi initiates early transcriptional re-programming in macrophages that supports long-term suppression of inflammation.PLoS pathogens · 2023Article
- Borrelia burgdorferi Engages Mammalian Type I IFN Responses via the cGAS-STING Pathway.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Helicobacter pylori Infection Elicits Type I Interferon Response in Human Monocytes via Toll-Like Receptor 8 Signaling.Journal of immunology research · 2022Article
- Epidemiologic, Clinical and Immunological Consequences of Co-Infections during Canine Leishmaniosis.Animals : an open access journal from MDPI · 2021Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Phagocytosed Borrelia burgdorferi (Bb) induces inflammatory signals that differ both quantitatively and qualitatively from those generated by spirochetal lipoproteins interacting with Toll-like receptor (TLR) 1/2 on the surface of human monocytes. Of particular significance, and in contrast to lipoproteins, internalized spirochetes induce transcription of IFN-β. Using inhibitory immunoregulatory DNA sequences (IRSs) specific to TLR7, TLR8, and TLR9, we show that the TLR8 inhibitor IRS957 significantly diminishes production of TNF-α, IL-6, and IL-10 and completely abrogates transcription of IFN-β in Bb-stimulated monocytes. We demonstrate that live Bb induces transcription of TLR2 and TLR8, whereas IRS957 interferes with their transcriptional regulation. Using confocal and epifluorescence microscopy, we show that baseline TLR expression in unstimulated monocytes is greater for TLR2 than for TLR8, whereas expression of both TLRs increases significantly upon stimulation with live spirochetes. By confocal microscopy, we show that TLR2 colocalization with Bb coincides with binding, uptake, and formation of the phagosomal vacuole, whereas recruitment of both TLR2 and TLR8 overlaps with degradation of the spirochete. We provide evidence that IFN regulatory factor (IRF) 7 is translocated into the nucleus of Bb-infected monocytes, suggesting its activation through phosphorylation. Taken together, these findings indicate that the phagosome is an efficient platform for the recognition of diverse ligands; in the case of Bb, phagosomal signaling involves a cooperative interaction between TLR2 and TLR8 in pro- and antiinflammatory cytokine responses, whereas TLR8 is solely responsible for IRF7-mediated induction of IFN-β.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.