ArticleJournal of leukocyte biology2016
FcγR mediates TLR2- and Syk-dependent NLRP3 inflammasome activation by inactivated Francisella tularensis LVS immune complexes.
Article in Journal of leukocyte biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
The trial behind it
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
16 citing papers in PubMed, 19 citations in OpenAlex.
- Differential Cell-Specific, Regulatory Roles of Fc γ Receptor IIB through IgG in IgA Nephropathy.Journal of the American Society of Nephrology : JASN · 2026Article
- Toll-like Receptor 2-Melatonin Feedback Loop Regulates the Activation of Spinal NLRP3 Inflammasome in Morphine-Tolerant Rats.Neurochemical research · 2023Article
- Nlrp3 Increases the Host's Susceptibility to Tularemia.Frontiers in microbiology · 2021Article
- Programmed Cell Death in the Evolutionary Race against Bacterial Virulence Factors.Cold Spring Harbor perspectives in biology · 2020Review
- Fcγ receptors and toll-like receptor 9 synergize to drive immune complex-induced dendritic cell maturation.Cellular immunology · 2019Article
- Inhibition of Francisella tularensis phagocytosis using a novel anti-LPS scFv antibody fragment.Scientific reports · 2019Article
- The inflammatory function of human IgA.Cellular and molecular life sciences : CMLS · 2019Review
- Innate Immune Recognition: An Issue More Complex Than Expected.Frontiers in cellular and infection microbiology · 2019Review
- Cytosolic Recognition of Microbes and Pathogens: Inflammasomes in Action.Microbiology and molecular biology reviews : MMBR · 2018Review
- The outer membrane protein Tp92 of Treponema pallidum induces human mononuclear cell death and IL-8 secretion.Journal of cellular and molecular medicine · 2018Article
- FcαRI co-stimulation converts human intestinal CD103Nature communications · 2018Article
- Checks and Balances between Autophagy and Inflammasomes during Infection.Journal of molecular biology · 2018Review
- Levistilide A Ameliorates NLRP3 Expression Involving the Syk-p38/JNK Pathway and Peripheral Obliterans in Rats.Mediators of inflammation · 2018Article
- Murine macrophage TLR2-FcγR synergy via FcγR licensing of IL-6 cytokine mRNA ribosome binding and translation.PloS one · 2018Article
- Oxidized Low-Density Lipoprotein Immune Complex Priming of the Nlrp3 Inflammasome Involves TLR and FcγR Cooperation and Is Dependent on CARD9.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Selenoprotein K regulation of palmitoylation and calpain cleavage of ASAP2 is required for efficient FcγR-mediated phagocytosis.Journal of leukocyte biology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
IgG (mAb)-opsonized, inactivated Francisella tularensis LVS (iFt-mAb) enhances TLR2-dependent IL-6 production by macrophages via Fcγ receptors (FcγR). In mice, vaccination with iFt-mAb provides IgA-dependent protection against lethal challenge with Ft LVS. Because inflammasome maturation of IL-1β is thought important for antibody-mediated immunity, we considered the possibility that iFt-mAb elicits an FcγR-dependent myeloid cell inflammasome response. Herein, we find that iFt-mAb enhances macrophage and dendritic cell IL-1β responses in a TLR2- and FcγR-dependent fashion. Although iFt-mAb complexes bind FcγR and are internalized, sensing of cytosolic DNA by absent in melanoma 2 (AIM2) is not required for the IL-1β response. In contrast, ASC, caspase-1, and NLR family pyrin domain-containing 3 (NLRP3) are indispensable. Further, FcγR-mediated spleen tyrosine kinase (Syk) signaling is required for this NLRP3-dependent IL-1β response, but the alternative IL-1β convertase caspase-8 is insufficient. Finally, iFt-mAb-vaccinated wild-type mice exhibit a significant delay in time to death, but IL-1R1- or Nlrp3-deficient mice vaccinated in this way are not protected and lack appreciable Francisella-specific antibodies. This study demonstrates that FcγR-mediated Syk activation leads to NLRP3 inflammasome-dependent IL-1β production in macrophages and suggests that an Nlrp3- and IL-1R-dependent process contributes to the IgA response important for protection against Ft LVS. These findings extend our understanding of cellular responses to inactivated pathogen-opsonized vaccine, establish FcγR-elicited Syk kinase-mediated NLRP3 inflammasome activation, and provide additional insight toward understanding crosstalk between TLR and FcγR signals.
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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.