Abstract
BackgroundMast 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 FindingsIn 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.ConclusionWe 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.
Highlights
Asthma is a complex clinical syndrome with airway hyperresponsiveness, tissue remodeling and chronic airway inflammation as the major characteristics
We find that prolonged exposure of mast cells to pathogens/Toll-like receptors (TLRs)-ligands modulates their effector responses by priming them for increased release of several inflammatory mediators when subsequently activated by IgE-receptors
There was a tendency for higher expression of TLR2, TLR4 and TLR6 in both phenotypes and TLR3 and TLR4 were significantly higher expressed in the connective tissue like mast cells (CTLMC) than mucosal like mast cells (MLMC)
Summary
Asthma is a complex clinical syndrome with airway hyperresponsiveness, tissue remodeling and chronic airway inflammation as the major characteristics. It is today well recognized that mast cell activation and concomitant release of mast cell mediators contribute to these pathological features [1]. In addition to histamine and CysLTs, other mast cell-derived mediators as proteases, prostaglandins and other eicosanoids, cytokines, chemokines and growth factors might promote different phases of the pathology, such as remodeling and inflammation [1,3,4,5]. Since mast cell mediators are tightly connected to asthma, both airway obstruction and inflammation, one reasonable speculation would be that mast cell reactivity is increased upon infection. 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
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