FcεR1-Mediated Mast Cell Reactivity Is Amplified through Prolonged Toll-Like Receptor-Ligand Treatment

Background Mast cell-derived mediators mediate several of the pathological features of asthma. Microbial infections induce asthma exacerbations in which the contribution of mast cells remains incomprehensible. Principal Findings In this study we have investigated the characteristic expression pattern of Toll-like receptors (TLRs) 1–9 and the effect of TLR ligand treatment on IgE-receptor mediated mast cell reactivity. For the studies we employed in vitro differentiated connective tissue like mast cells (CTLMC) and mucosal like mast cells (MLMC) from mice. Both phenotypes were treated for 24 h or 96 h with ligands for TLR1/2, TLR2/6, TLR3 and TLR4, before activation with IgE and antigen. Prolonged exposure (96 h) with TLR-ligands promoted mast cell reactivity following IgE-receptor activation. TLR4 activation with LPS generated the most pronounced effect, with an enhanced degranulation and secretion of leukotrienes, cytokines and chemokines, in both CTLMC and MLMC. The effect of LPS was mediated through a Myd88-dependent pathway and the increased effect involved JNK-dependent pathway. Conclusion We find that prolonged exposure of mast cells to pathogens/TLR-ligands modulates their effector responses by priming them for increased release of several inflammatory mediators when subsequently activated by IgE-receptors. These data suggest that infections might exaggerate the severity of allergic reactions such as in asthma, by enhancing mediator release from mast cells.

• Publication year

  2012

• Venue

  PLoS ONE

• Publication date

  2012-08-16

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0043547PMID 22916277PMCID 3420882
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• First influenza season after the 2009 pandemic influenza: characteristics of intensive care unit admissions in adults and children in Vall d'Hebron Hospital.

  2012cited by this paper
• Lipopolysaccharide enhances FcɛRI‐mediated mast cell degranulation by increasing Ca2+ entry through store‐operated Ca2+ channels: implications for lipopolysaccharide exacerbating allergic asthma

  2012cited by this paper
• Mast cell phenotype, location, and activation in severe asthma. Data from the Severe Asthma Research Program.

  2011cited by this paper
• The Effect of Bacterial, Viral and Fungal Infection on Mast Cell Reactivity in the Allergic Setting

  2011cited by this paper
• Mast cell-orchestrated immunity to pathogens

  2010cited by this paper
• Role of viral respiratory infections in asthma and asthma exacerbations

  2010cited by this paper
• TLR2/MyD88-Dependent and -Independent Activation of Mast Cell IgE Responses by the Skin Commensal Yeast Malassezia sympodialis1

  2009cited by this paper
• A TLR2 Ligand Suppresses Allergic Inflammatory Reactions by Acting Directly on Mast Cells

  2009cited by this paper
• Murine mast cells secrete a unique profile of cytokines and prostaglandins in response to distinct TLR2 ligands

  2009influential reference
• Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does not lead to differential signaling

  2008cited by this paper
• Role of mast cells in airway remodeling.

  2007cited by this paper
• Stimulation of mast cells via FcεR1 and TLR2: The type of ligand determines the outcome

  2007cited by this paper
• Lipoteichoic acid downregulates FcepsilonRI expression on human mast cells through Toll-like receptor 2.

  2007cited by this paper
• FcepsilonRI aggregation promotes survival of connective tissue-like mast cells but not mucosal-like mast cells.

  2007cited by this paper
• Lipoteichoic acid downregulates FcεRI expression on human mast cells through Toll-like receptor 2

  2007cited by this paper
• Chymase-positive mast cells play a role in the vascular component of airway remodeling in asthma.

  2007cited by this paper
• FcεRI Aggregation Promotes Survival of Connective Tissue-Like Mast Cells but Not Mucosal-Like Mast Cells1

  2007cited by this paper
• Stimulation of mast cells via FcvarepsilonR1 and TLR2: the type of ligand determines the outcome.

  2007cited by this paper
• Infections and asthma.

  2006cited by this paper
• Pathogen recognition and innate immunity.

  2006cited by this paper
• FcepsilonR1 and toll-like receptors mediate synergistic signals to markedly augment production of inflammatory cytokines in murine mast cells.

  2006influential reference
• The role of the mast cell in the pathophysiology of asthma.

  2006cited by this paper
• Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children

  2005cited by this paper
• TLR3-, TLR7-, and TLR9-Mediated Production of Proinflammatory Cytokines and Chemokines from Murine Connective Tissue Type Skin-Derived Mast Cells but Not from Bone Marrow-Derived Mast Cells 1

  2004cited by this paper
• Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3.

  2004cited by this paper
• Toll‐like receptor stimulation induces airway hyper‐responsiveness to bradykinin, an effect mediated by JNK and NF‐κB signaling pathways

  2004cited by this paper
• Toll-like receptor stimulation induces airway hyper-responsiveness to bradykinin, an effect mediated by JNK and NF-kappa B signaling pathways.

  2004cited by this paper
• Cutting Edge: Distinct Toll-Like Receptor 2 Activators Selectively Induce Different Classes of Mediator Production from Human Mast Cells 12

  2003cited by this paper
• Toll‐like receptor 2 (TLR2) and TLR4 differentially activate human mast cells

  2003cited by this paper
• Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity.

  2002cited by this paper
• Toll‐like receptor 4‐mediated activation of murine mast cells

  2001cited by this paper
• Protective Roles of Mast Cells Against Enterobacterial Infection Are Mediated by Toll-Like Receptor 41

  2001cited by this paper
• Rhinovirus and respiratory syncytial virus in wheezing children requiring emergency care. IgE and eosinophil analyses.

  1999cited by this paper
• Combined antagonism of leukotrienes and histamine produces predominant inhibition of allergen-induced early and late phase airway obstruction in asthmatics.

  1997cited by this paper
• A common cold virus, rhinovirus 16, potentiates airway inflammation after segmental antigen bronchoprovocation in allergic subjects.

  1994cited by this paper
• [Infections and asthma].

  1986cited by this paper

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  2024cites this paper
• Uncovering the Mast Cell Response to Mycobacterium tuberculosis

  2022cites this paper
• Interactions between Macrophages and Mast Cells in the Female Reproductive System

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• LPS Guides Distinct Patterns of Training and Tolerance in Mast Cells

  2022cites this paper
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  2020cites this paper
• The Response of Tissue Mast Cells to TLR3 Ligand Poly(I:C) Treatment

  2020influential citation
• Mast Cells

  2020cites this paper
• Protective and pathogenic roles for mast cells during viral infections

  2020cites this paper
• Regulation of the pleiotropic effects of tissue-resident mast cells.

  2019cites this paper
• Mast Cells and Their Progenitors in Allergic Asthma

  2019cites this paper
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  2019cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
• Changing the threshold—Signals and mechanisms of mast cell priming

  2018cites this paper
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  2017cites this paper
• DNA methylation of Th2 lineage determination genes at birth is associated with allergic outcomes in childhood

  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2015cites this paper
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  2014cites this paper
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  2014cites this paper
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  2013cites this paper
• Toll-like receptors 3 ligation directly and indirectly affects mast cell cysteinyl leukotriene generation

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• Mast cells and vascular diseases.

  2013cites this paper
• Innate Immunity and Its Regulation by Mast Cells

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