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Lipopolysaccharide suppresses IgE‐mast cell‐mediated reactions
Author(s) -
Wang N.,
McKell M.,
Dang A.,
Yamani A.,
Waggoner L.,
Vai S.,
Noah T.,
Wu D.,
Kordowski A.,
Köhl J.,
Hoebe K.,
Divanovic S.,
Hogan S. P.
Publication year - 2017
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13013
Subject(s) - immunoglobulin e , desensitization (medicine) , lipopolysaccharide , mast cell , immunology , anaphylaxis , chemistry , tlr4 , allergy , inflammation , antibody , receptor , biology , biochemistry
Summary Background Clinical and experimental analyses have identified a central role for IgE/Fcε RI /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 C57 BL /6 WT , tlr4 −/− and IL 10 −/− 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, Ca 2+ ‐mobilization and the expression of Fcε RI on peritoneal MC s were quantitated. Results We show that LPS exposure of C57 BL /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 Fcε RI on MC s and loss of sensitivity to IgE activation. Notably, LPS ‐induced desensitization of MC s was short term with MC sensitivity to IgE reconstituted within 48 hours, which was associated with recapitulation of Fcε RI expression on the MC s. Mechanistic analyses revealed a requirement for IL ‐10 in LPS ‐mediated decrease in MC Fcε RI surface expression. Conclusions & Clinical Relevance Collectively, these studies suggest that LPS ‐induced IL ‐10 promotes the down‐regulation of MC surface Fcε RI 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.