Lipopolysaccharide suppresses IgE-mast cell-mediated reactions.

ABSTRACT: Clinical and experimental analyses have identified a central role for IgE/Fc?RI/mast cells in promoting IgE-mediated anaphylaxis. Recent data from human studies suggest that bacterial infections can alter susceptibility to anaphylaxis.We examined the effect of LPS exposure on the induction of IgE-mast cell (MC) mediated reactions in mice.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 Fc?RI on peritoneal MCs were quantitated.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 Fc?RI 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 Fc?RI expression on the MCs. Mechanistic analyses revealed a requirement for IL-10 in LPS-mediated decrease in MC Fc?RI surface expression.Collectively, these studies suggest that LPS-induced IL-10 promotes the down-regulation of MC surface Fc?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.

SUBMITTER: Wang N 

PROVIDER: S-EPMC5865592 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature