Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3

Kulka, Marianna; Alexopoulou, Lena; Flavell, Richard A.; Metcalfe, Dean D.

doi:10.1016/j.jaci.2004.03.049

Cited by 312 publications

(347 citation statements)

References 33 publications

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“…20 One previous report indicated that TLR5 recognizes flagellin. 21,22 We thus took another approach to elucidate if flagellin activated mast cell via acting on TLR5 to elicit the release of inflammatory mediators that might contribute to the initiation of mucosal inflammation. Anti-flagellin antibody-or antiFc␥RI antibody-precipitated moMC cellular extracts (as mentioned in Figure 2A) was processed by immune blotting.…”

Section: Flagellin-specific Immune Response Induces Momcs To Release mentioning

confidence: 99%

Fc Gamma Receptor Signaling in Mast Cells Links Microbial Stimulation to Mucosal Immune Inflammation in the Intestine

Chen

Feng

Zheng

et al. 2008

The American Journal of Pathology

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Microbes and microbial products are closely associated with the pathogenesis of inflammatory bowel disease (IBD); however, the mechanisms behind this connection remain unclear. It has been previously reported that flagellin-specific antibodies are increased in IBD patient sera. As mastocytosis is one of the pathological features of IBD, we hypothesized that flagellin-specific immune responses might activate mast cells that then contribute to the initiation and maintenance of intestinal inflammation. Thirtytwo colonic biopsy samples were collected from IBD patients. A flagellin/flagellin-specific IgG/Fc gamma receptor I complex was identified on biopsied mast cells using both immunohistochemistry and co-immunoprecipitation experiments; this complex was shown to co-localize on the surfaces of mast cells in the colonic mucosa of patients with IBD. In addition, an ex vivo study showed flagellin-IgG was able to bind to human mast cells. These cells were found to be sensitized to flagellin-specific IgG; re-exposure to

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Section: Flagellin-specific Immune Response Induces Momcs To Release mentioning

confidence: 99%

Fc Gamma Receptor Signaling in Mast Cells Links Microbial Stimulation to Mucosal Immune Inflammation in the Intestine

Chen

Feng

Zheng

et al. 2008

The American Journal of Pathology

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“…However, the antigen-mediated response may be markedly influenced by co-activation through other cell surface receptors and it has been suggested that these interactions may modulate mast celldriven reactions in situ [2,3]. Such receptors, which have been reported to induce mediator release by themselves, enhance antigen-mediated mast cell activation, or inhibit antigen-mediated mast cell activation, include the stem cell factor (SCF) receptor, Kit [4,5]; toll-like receptors (TLRs) such as TLR2 [6,7], TLR3 [8], and TLR4 [7,9]; and G protein-coupled receptors (GPCRs) [10] such as receptors for adenosine (A3 receptor) [11][12][13], macrophage inflammatory protein-1α (CCR1) [14], the complement component C3a (C3aR) [15], sphingosine-1-phosphate (SIP) (S1P 2 R) [16] and prostaglandin (PG)E 2 (EP1 and 3) [17][18][19]. It is unclear, however, how the signaling cascades initiated by these various classes of receptors are integrated with FcεRI-mediated signals to modify antigen-mediated mast cell activation.…”

Section: Introductionmentioning

confidence: 99%

Synergistic activation of phospholipases Cγ and Cβ: A novel mechanism for PI3K-independent enhancement of FcεRI-induced mast cell mediator release

Kuehn

Beaven

et al. 2008

Cellular Signalling

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Antigen/IgE-mediated mast cell activation via FcεRI can be markedly enhanced by the activation of other receptors expressed on mast cells and these receptors may thus contribute to the allergic response in vivo. One such receptor family is the G protein-coupled receptors (GPCRs). Although the signaling cascade linking FcεRI aggregation to mast cell activation has been extensively investigated, the mechanisms by which GPCRs amplify this response are relatively unknown. To investigate this, we utilized prostaglandin (PG)E 2 based on initial studies demonstrating its greater ability to augment antigen-mediated degranulation in mouse mast cells than other GPCR agonists examined. This enhancement, and the ability of PGE 2 to amplify antigen-induced calcium mobilization, was independent of phosphoinositide 3-kinase but was linked to a pertussis toxinsensitive synergistic translocation to the membrane of phospholipase (PL)Cγ and PLCβ and to an enhancement of PLCγ phosphorylation. This "trans-synergistic" activation of PLCβ and γ, in turn, enhanced production of inositol 1,4,5-trisphosphate, store operated calcium entry, and activation of protein kinase C (PKC) (α and β). These responses were critical for the promotion of degranulation. This is the first report of synergistic activation between PLCγ and PLCβ that permits reinforcement of signals for degranulation in mast cells.

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“…TLR5 engagement by bacterial flagellin activates the MyD88-dependent signaling pathway, which leads to the nuclear translocation of NF-B and the activation of the MAPKs, ultimately inducing the maturation of antigen-presenting cells and the secretion of proinflammatory cytokines and chemokines (4)(5)(6)(7)(8). TLR5 is expressed by a variety of cells including monocytes, dendritic cells (DCs), epithelial cells, and mast cells (5,(9)(10)(11)(12)(13). Interestingly, TLR5 is expressed on the basolateral side of intestinal epithelial cells, which are chronically exposed to commensal bacteria (6,14), but it is expressed on the apical side of lung epithelial cells, which are usually not exposed to microorganisms (15).…”

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confidence: 99%

Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria

Feuillet

Medjane

Mondor

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Toll-like receptors (TLRs) are key components of the immune system that detect microbial infection and trigger antimicrobial host defense responses. TLR5 is a sensor for monomeric flagellin, which is a component of bacterial flagella known to be a virulence factor. In this study we generated TLR5-deficient mice and investigated the role of TLR5 signaling in the detection of flagellin and antibacterial immune responses to Salmonella typhimurium and Pseudomonas aeruginosa. We found that TLR5 is essential for the recognition of bacterial flagellin both in vivo and ex vivo. TLR5 contribution to antibacterial host response to i.p. infection with S. typhimurium or intranasal administration of P. aeruginosa may be masked by TLR4 or other sensing mechanisms. By using radiation bone marrow chimera, we showed that upon i.p. injection of flagellin immune responses are mediated by lymphoid cells, whereas resident cells are required for the initiation of response upon intranasal flagellin administration. These results suggest that flagellin recognition in different organs is mediated by distinct TLR5-expressing cells and provide insights into the cooperation of the TLR5 and TLR4 signaling pathways used by the innate immune system in the recognition of bacterial pathogens.bacterial infection ͉ flagellin R ecognition of microbial infection and initiation of immune response are controlled by multiple mechanisms. Toll-like receptors (TLRs) have recently emerged as key components of the innate immune system that recognize common molecular structures detected in certain groups of microorganisms and trigger the activation of adaptive immunity (1). Each TLR detects specific microbial components. For example, TLR4 recognizes LPS, TLR2 recognizes bacterial lipoproteins and lipoteichoic acid, and TLR3 recognizes viral double-stranded RNA. All TLRs share a common intracellular domain, the Toll-IL-1 receptor homology domain, and upon activation initiate signaling cascades that lead to common responses such as the induction of inflammatory cytokines and up-regulation of costimulatory molecules. Moreover, TLRs also have specific functions as exemplified by their different ability to induce type I IFN (1). Thus, TLRs activate multiple steps in the inflammatory reactions that help to eliminate the invading pathogens and coordinate systemic defenses.Among TLRs, TLR5 is the receptor for flagellin, the major constituent of bacterial flagella and a virulence factor for Gramnegative and Gram-positive bacteria (2, 3). TLR5 engagement by bacterial flagellin activates the MyD88-dependent signaling pathway, which leads to the nuclear translocation of NF-B and the activation of the MAPKs, ultimately inducing the maturation of antigen-presenting cells and the secretion of proinflammatory cytokines and chemokines (4-8). TLR5 is expressed by a variety of cells including monocytes, dendritic cells (DCs), epithelial cells, and mast cells (5, 9-13). Interestingly, TLR5 is expressed on the basolateral side of intestinal epithelial cells, which are chronicall...

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Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3

Cited by 312 publications

References 33 publications

Fc Gamma Receptor Signaling in Mast Cells Links Microbial Stimulation to Mucosal Immune Inflammation in the Intestine

Fc Gamma Receptor Signaling in Mast Cells Links Microbial Stimulation to Mucosal Immune Inflammation in the Intestine

Synergistic activation of phospholipases Cγ and Cβ: A novel mechanism for PI3K-independent enhancement of FcεRI-induced mast cell mediator release

Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria

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