A TLR2 Ligand Suppresses Allergic Inflammatory Reactions by Acting Directly on Mast Cells

Background: Although much attention has been focused on the anti-allergic effects of probiotics, their mode of action is not fully understood. Mast cells, which play a central role in inducing allergic inflammation, are potential targets of probiotics given the recent discovery that they express Toll-like receptors (TLRs), the pattern recognition receptors for microbial components. In this study, we examined whether allergic reactions of mast cells are modulated by stimulation through TLR2. Methods: The effects on mast cells of the synthetic TLR2 ligand Pam3CSK4 and Bifidobacterium pseudocatenulatum JCM 7041 were evaluated in vitro. Furthermore, the effects of Pam3CSK4 on mast cell-induced increase in vascular permeability in vivo were investigated by employing mast cell-deficient W/W-v mice into which IgE-sensitized mouse bone marrow-derived mast cells were transferred. Results: Pam3CSK4 and Bifidobacterium pseudocatenulatum JCM 7041 suppressed degranulation of IgE-sensitized mast cells upon antigen stimulation in vitro. Pam3CSK4 also suppressed leukotriene C-4 production triggered by engagement of the high-affinity IgE receptor, Fc epsilon RI. Intracellular Ca2+ mobilization and phosphorylation of Erk were suppressed by pretreatment with Pam3CSK4, suggesting that the TLR2 ligand suppresses activation of mast cells by interrupting Fc epsilon RI-mediated intracellular signaling. Pam3CSK4 treatment of bone marrow-derived mast cells reduced the increase in vascular permeability in recipient W/W-v mice upon intravenous injection of antigen; the decrease was by about half, in a TLR-dependent manner. Conclusion: Collectively, these results demonstrate that the Fc epsilon RI-mediated inflammatory responses of mast cells are suppressed by stimulation through TLR2, suggesting that probiotics exert potential anti-allergic effects, at least in part, through direct effects on mast cells. Copyright (C) 2009 S. Karger AG, Basel