Lipopolysaccharide suppresses IgE-mast cell-mediated reactions

N. Wang, M. McKell, A. Dang, A. Yamani, L. Waggoner, S. Vanoni, T. Noah, D. Wu, A. Kordowski, J. Köhl, K. Hoebe, S. Divanovic, S. P. Hogan*

*Korrespondierende/r Autor/-in für diese Arbeit
2 Zitate (Scopus)


Background: Clinical and experimental analyses have identified a central role for IgE/FcεRI/mast cells in promoting IgE-mediated anaphylaxis. Recent data from human studies suggest that bacterial infections can alter susceptibility to anaphylaxis. Objective: We examined the effect of LPS exposure on the induction of IgE-mast cell (MC) mediated reactions in mice. Methods: C57BL/6 WT, tlr4−/− and IL10−/− mice were exposed to LPS, and serum cytokines (TNF and IL-10) were measured. Mice were subsequently treated with anti-IgE, and the symptoms of passive IgE-mediated anaphylaxis, MC activation, Ca2+-mobilization and the expression of FcεRI on peritoneal MCs were quantitated. Results: We show that LPS exposure of C57BL/6 WT mice constraints IgE-MC–mediated reactions. LPS-induced suppression of IgE-MC–mediated responses was TLR-4-dependent and associated with increased systemic IL-10 levels, decreased surface expression of FcεRI on MCs and loss of sensitivity to IgE activation. Notably, LPS-induced desensitization of MCs was short term with MC sensitivity to IgE reconstituted within 48 hours, which was associated with recapitulation of FcεRI expression on the MCs. Mechanistic analyses revealed a requirement for IL-10 in LPS-mediated decrease in MC FcεRI surface expression. Conclusions & Clinical Relevance: Collectively, these studies suggest that LPS-induced IL-10 promotes the down-regulation of MC surface FcεRI expression and leads to desensitization of mice to IgE-mediated reactions. These studies indicate that targeting of the LPS-TLR-4-IL-10 pathway may be used as a therapeutic approach to prevent adverse IgE-mediated reactions.

ZeitschriftClinical and Experimental Allergy
Seiten (von - bis)1574-1585
PublikationsstatusVeröffentlicht - 01.12.2017


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