ArticleCell systems2017
Systematic Investigation of Multi-TLR Sensing Identifies Regulators of Sustained Gene Activation in Macrophages.
Article in Cell systems, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
- Lyn expression in macrophages promotes TLR activation and restricts proliferation in an isoform-independent manner.Journal of leukocyte biology · 2025Article
- Local therapy with combination TLR agonists stimulates systemic anti-tumor immunity and sensitizes tumors to immune checkpoint blockade.Oncoimmunology · 2024Article
- Avian Influenza Virus Tropism in Humans.Viruses · 2023Review
- Microscale combinatorial stimulation of human myeloid cells reveals inflammatory priming by viral ligands.Science advances · 2023Article
- SERTAD3 induces proteasomal degradation of ZIKV capsid protein and represents a therapeutic target.Journal of medical virology · 2023Article
- Epigenomics of conventional type-I dendritic cells depicted preferential control of TLR9 versus TLR3 response by NCoR1 through differential IRF3 activation.Cellular and molecular life sciences : CMLS · 2022Article
- Synergistic Effects of Toll-Like Receptor 1/2 and Toll-Like Receptor 3 Signaling Triggering Interleukin 27 Gene Expression in Chikungunya Virus-Infected Macrophages.Frontiers in cell and developmental biology · 2022Article
- Innate control of adaptive immunity and adaptive instruction of innate immunity: bi-directional flow of information.Current opinion in immunology · 2021Review
- The Transcription Factor SUB1 Is a Master Regulator of the Macrophage TLR Response in Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Review
- 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
- Babaodan controls excessive immune responses and may represent a cytokine-targeted agent suitable for COVID-19 treatment.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Article
- Engineering Supramolecular Organizing Centers for Optogenetic Control of Innate Immune Responses.Advanced biology · 2021Article
- Article
- A synthetic pathogen mimetic molecule induces a highly amplified synergistic immune responseChemical science · 2021Article
- Immunological design of commensal communities to treat intestinal infection and inflammation.PLoS pathogens · 2021Article
- Rotavirus Interactions With Host Intestinal Epithelial Cells.Frontiers in immunology · 2021Review
- Exploring the Role of TRIP-Brs in Human Breast Cancer: An Investigation of Expression, Clinicopathological Significance, and Prognosis.Molecular therapy oncolytics · 2020Article
- Pairwise Stimulations of Pathogen-Sensing Pathways Predict Immune Responses to Multi-adjuvant Combinations.Cell systems · 2020Article
- TLR2 on blood monocytes senses dengue virus infection and its expression correlates with disease pathogenesis.Nature communications · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A typical pathogen presents a combination of Toll-like receptor (TLR) ligands during infection. Although individual TLR pathways have been well characterized, the nature of this "combinatorial code" in pathogen sensing remains unclear. Here, we conducted a comprehensive transcriptomic analysis of primary macrophages stimulated with all possible pairwise combinations of four different TLR ligands to understand the requirements, kinetics, and outcome of combined pathway engagement. We find that signal integration between TLR pathways leads to non-additive responses for a subset of immune mediators with sustained expression (>6 hr) properties and T cell polarizing function. To identify the underlying regulators, we conducted a focused RNAi screen and identified four genes-Helz2, Phf11d, Sertad3, and Zscan12-which preferentially affect the late phase response of TLR-induced immune effector expression. This study reveals key molecular details of how contemporaneous signaling through multiple TLRs, as would often be the case with pathogen infection, produce biological outcomes distinct from the single ligands typically used to characterize TLR 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.