ArticleThe Journal of biological chemistry2015
Spleen Tyrosine Kinase (Syk) Mediates IL-1β Induction by Primary Human Monocytes during Antibody-enhanced Dengue Virus Infection.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Insight Into Inflammasome Signaling: Implications forFrontiers in immunology · 2020Pooled it
- Antibody-Dependent Enhancement in Flavivirus Infections: From Fc Receptor Signaling to Vaccine and Therapeutic Design.Viruses · 2026Review
- Unique molecular profiling of monocyte responses to a high dose of DENV-NS1 reflected the effect of NS1 on hemostasis.Medical microbiology and immunology · 2026Article
- Functional Antibody-Dependent Enhancement as an Immune Assessment Platform: Development, Standardization, and Translational Interpretation in Flavivirus Research.Pathogens (Basel, Switzerland) · 2026Review
- The contributions of TLR2, TLR8 and TLR3 to direct and antibody-dependent enhancement of dengue virus serotype 2 infection.Npj viruses · 2026Article
- Targeting a specific subset of neutrophils to mitigate cardiac reperfusion injury.Research square · 2025Article
- In-silico discovery of druggable molecular signatures that drive dengue fever to severe dengue fever highlighting common pathogenesis through single-cell RNA-Seq analysis.Scientific reports · 2025Article
- Exploiting host kinases to combat dengue virus infection and disease.Antiviral research · 2025Review
- The inflammasome pathway is activated by dengue virus non-structural protein 1 and is protective during dengue virus infection.PLoS pathogens · 2024Article
- Article
- Vav proteins do not influence dengue virus replication but are associated with induction of phospho-ERK, IL-6, and viperin mRNA following DENV infectionMicrobiology spectrum · 2024Article
- Multiple receptor tyrosine kinases regulate dengue infection of hepatocytes.Frontiers in cellular and infection microbiology · 2024Article
- Src- and Abl-family kinases activate spleen tyrosine kinase to maximize phagocytosis and Leishmania infection.Journal of cell science · 2023Article
- Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality.International reviews of immunology · 2022Article
- Ross River Virus Immune Evasion Strategies and the Relevance to Post-viral Fatigue, and Myalgic Encephalomyelitis Onset.Frontiers in medicine · 2021Article
- Emergence of Dengue 4 as Dominant Serotype During 2017 Outbreak in South India and Associated Cytokine Expression Profile.Frontiers in cellular and infection microbiology · 2021Article
- Differential Expression of Human MicroRNAs During Dengue Virus Infection in THP-1 Monocytes.Frontiers in cellular and infection microbiology · 2021Article
- Molecular basis of carrageenan-induced cytokines production in macrophages.Cell communication and signaling : CCS · 2020Article
- Inflammasome Fuels Dengue Severity.Frontiers in cellular and infection microbiology · 2020Review
- Dengue Virus Serotype 2 and Its Non-Structural Proteins 2A and 2B Activate NLRP3 Inflammasome.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Approximately 500,000 people are hospitalized with severe dengue illness annually. Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is believed to contribute to the pathogenic cytokine storm described in severe dengue patients, but the precise signaling pathways contributing to elevated cytokine production are not elucidated. IL-1β is a potent inflammatory cytokine that is frequently elevated during severe dengue, and the unique dual regulation of IL-1β provides an informative model to study ADE-induced cytokines. This work utilizes patient-derived anti-DENV mAbs and primary human monocytes to study ADE-induced IL-1β and other cytokines. ADE of DENV serotype 2 (DENV-2) elevates mature IL-1β secretion by monocytes independent of DENV replication by 4 h postinoculation (hpi). Prior to this, DENV immune complexes activate spleen tyrosine kinase (Syk) within 1 hpi. Syk induces elevated IL1B, TNF, and IL6 mRNA by 2 hpi. Syk mediates elevated IL-1β secretion by activating ERK1/2, and both Syk and ERK1/2 inhibitors ablated ADE-induced IL-1β secretion. Maturation of pro-IL-1β during ADE requires caspase-1 and NLRP3, but caspase-1 is suboptimally increased by ADE and can be significantly enhanced by a typical inflammasome agonist, ATP. Importantly, this inflammatory Syk-ERK signaling axis requires DENV immune complexes, because DENV-2 in the presence of serotype-matched anti-DENV-2 mAb, but not anti-DENV-1 mAb, activates Syk, ERK, and IL-1β secretion. This study provides evidence that DENV-2 immune complexes activate Syk to mediate elevated expression of inflammatory cytokines. Syk and ERK may serve as new therapeutic targets for interfering with ADE-induced cytokine expression during severe dengue.
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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.