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.


RESULTS
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.


CONCLUSIONS
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.
Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Rohit
R
Saluja
Ingrid
I
Delin
Gunnar P
GP
Nilsson
Mikael
M
Adner
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D017455:Receptors, IgE / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists*
D018925:Chemokines; D016207:Cytokines; D015289:Leukotrienes; D008070:Lipopolysaccharides; D017455:Receptors, IgE; D051193:Toll-Like Receptors