ArticleInternational immunology2015
Toll-like receptor 9 trafficking and signaling for type I interferons requires PIKfyve activity.
Article in International immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon.Mucosal immunology · 2018Trial
- Review
- Bidirectional crosstalk between TRP channels and Toll-like receptors in inflammation and host defense.Journal of neuroinflammation · 2026Review
- An Integrative Framework Identifies Cooperative Targeting of Host Pathways by Tick Salivary miRNAs.Computational and structural biotechnology journal · 2026Article
- Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms.Journal of biomedical science · 2025Review
- GWAS reveals genetic basis of a predisposition to severe COVID-19 throughFrontiers in medicine · 2023Article
- An AP-3-dependent pathway directs phagosome fusion with Rab8 and Rab11 vesicles involved in TLR2 signaling.Traffic (Copenhagen, Denmark) · 2022Article
- Regulation of the nucleic acid-sensing Toll-like receptors.Nature reviews. Immunology · 2022Review
- CpG ODN as an adjuvant arouses the vigor of B cells by relieving the negative regulation of surface TLR9 to enhance the antibody response to vaccine.Applied microbiology and biotechnology · 2021Article
- Viruses and Endogenous Retroviruses as Roots for Neuroinflammation and Neurodegenerative Diseases.Frontiers in neuroscience · 2021Review
- RUNX Binding Sites Are Enriched in Herpesvirus Genomes, and RUNX1 Overexpression Leads to Herpes Simplex Virus 1 Suppression.Journal of virology · 2020Article
- miR32-5p promoted vascular smooth muscle cell calcification by upregulating TNFα in the microenvironment.BMC immunology · 2020Article
- Protein Dynamics in Cytosolic DNA-Sensing Antiviral Innate Immune Signaling Pathways.Frontiers in immunology · 2020Review
- Below the surface: The inner lives of TLR4 and TLR9.Journal of leukocyte biology · 2019Review
- The sensing of mitochondrial DAMPs by non-immune cells.Cell stress · 2019Review
- The interaction between IKKα and LC3 promotes type I interferon production through the TLR9-containing LAPosome.Science signaling · 2018Article
- BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells.Nature communications · 2017Article
- IRAPNature immunology · 2017Article
- Microbe-inducible trafficking pathways that control Toll-like receptor signaling.Traffic (Copenhagen, Denmark) · 2017Review
- Molecular mechanisms of regulation of Toll-like receptor signaling.Journal of leukocyte biology · 2016Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Toll-like receptors (TLRs) traffic to distinct membranes for signaling. TLR7 and TLR9 recognize viral nucleic acids in the endosomes and induce robust anti-viral program. Signaling from these TLRs bifurcate at the level of distinct endosomal compartments, namely VAMP3(+) and LAMP(+) endosomes, to mediate the induction of cytokine and type I interferon (IFN) genes, respectively. The formation of the TLR9 endosome competent for IFNs induction requires AP-3. Phosphoinositides (PIs) mark distinct subcellular membranes and control membrane trafficking. However, their role in TLR trafficking and signaling in different dendritic cell (DC) subsets remains unclear. Here, we examined the role of phosphatidylinositol 3P 5-kinase, PIKfyve, in TLR9 trafficking and signaling. We demonstrate that inhibition of PIKfyve activity preferentially blocks TLR9 signaling for type I IFN induction in FLT3L-bone marrow-derived DCs. By confocal microscopy using RAW264.7 cells, we show that trafficking of both TLR9 and CpG to the LAMP1(+) compartment was blocked by PIKfyve inhibitor treatment, whereas their trafficking to the VAMP3(+) endosome remained intact. Further, AP-3 recruitment to TLR9 endosomes was impaired by PIKfyve inhibition. These data indicate that PIKfyve provides critical PIs necessary for the formation of endosome from which TLR9 signals to induce type I IFNs.
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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.