ArticleScience signaling2016
Innate immune memory and homeostasis may be conferred through crosstalk between the TLR3 and TLR7 pathways.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Epigenetic profiling reveals M1 macrophages as the primary drivers of trained immunity in HSV-1 latently infected mice.PLoS pathogens · 2026Article
- Quantitative Modeling of TLR Signaling Reveals Missing Negative Feedback Guiding Identification of TANK-IKKε Checkpoint.bioRxiv : the preprint server for biology · 2026Article
- Central Role of Toll-like Receptor-9 Gene Function in Inflammation-Mediated Neuronal Plasticity: Implications for Long-Term Memory Development.Molecular neurobiology · 2025Review
- Article
- Targeting toll-like receptors: unveiling potential therapeutic strategies for deep vein thrombosis.Frontiers in immunology · 2025Review
- Catch me if you can: viral nucleic acids to host sensors.Frontiers in immunology · 2025Review
- ISRES+: an improved evolutionary strategy for function minimization to estimate the free parameters of systems biology models.Bioinformatics (Oxford, England) · 2023Article
- Article
- Toll-like receptor 3 neuroimmune signaling and behavior change: A strain comparison between Lewis and Wistar rats.Behavioural brain research · 2023Article
- Regulation of the double-stranded RNA response through ADAR1 licenses metaplastic reprogramming in gastric epithelium.JCI insight · 2022Article
- Two Faces of Macrophages: Training and Tolerance.Biomedicines · 2021Review
- TLR7 ligation augments hematopoiesis in Rps14 (uS11) deficiency via paradoxical suppression of inflammatory signaling.Blood advances · 2021Article
- Intratumoral combination therapy with poly(I:C) and resiquimod synergistically triggers tumor-associated macrophages for effective systemic antitumoral immunity.Journal for immunotherapy of cancer · 2021Article
- Inhalable nanovaccine with biomimetic coronavirus structure to trigger mucosal immunity of respiratory tract against COVID-19.Chemical engineering journal (Lausanne, Switzerland : 1996) · 2021Article
- Role of toll-like receptor 7 (TLR7) in voluntary alcohol consumption.Brain, behavior, and immunity · 2020Article
- Transcriptomics uncovers substantial variability associated with alterations in manufacturing processes of macrophage cell therapy products.Scientific reports · 2020Article
- Mechanisms of Action of Autophagy Modulators Dissected by Quantitative Systems Pharmacology Analysis.International journal of molecular sciences · 2020Article
- Arginine-Based Poly(I:C)-Loaded Nanocomplexes for the Polarization of Macrophages Toward M1-Antitumoral Effectors.Frontiers in immunology · 2020Article
- Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses.Cells · 2019Review
- Toll-like receptor 3 activation increases voluntary alcohol intake in C57BL/6J male mice.Brain, behavior, and immunity · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and stimulate the innate immune response through the production of cytokines. The innate immune response depends on the timing of encountering PAMPs, suggesting a short-term "memory." In particular, activation of TLR3 appears to prime macrophages for the subsequent activation of TLR7, which leads to synergistically increased production of cytokines. By developing a calibrated mathematical model for the kinetics of TLR3 and TLR7 pathway crosstalk and providing experimental validation, we demonstrated the involvement of the Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in controlling the synergistic production of cytokines. Signaling through this pathway played a dual role: It mediated the synergistic production of cytokines, thus boosting the immune response, and it also maintained homeostasis to avoid an excessive inflammatory response. Thus, we propose that the JAK-STAT pathway provides a cytokine rheostat mechanism, which enables macrophages to fine-tune their responses to multiple, temporally separated infection events involving the TLR3 and TLR7 pathways.
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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.