Immunocomplexes down-modulate the induction of food allergy in mouse. (97.12)

Abstract

Abstract Food allergy is an adverse Th2 response whose incidence has been increasing dramatically over the past decade. We have demonstrated that signaling triggered by immunocomplexes (IC) through CD16 (FcgRIII) in conjunction with TLR4 prime dendritic cells (DCs) to drive Th2 responses. To address our hypothesis that IgG plays a role in the pathogenesis of food allergy in a murine model, we investigated the contribution of CD16 signaling. Wild type (WT) or CD16-/- mice were sensitized by gavage for 8 weeks with SEB, SEB+OVA or SEB+OVA-IC and challenged on the 9th week. To analyze the systemic responses, blood eosinophilia and OVA-specific serum IgE and IgG1 levels were measured. We found that CD16-/- had reduced responses compared to WT, however, both SEB+OVA-IC-immunized WT and CD16-/- mice had lower responses compared to SEB+OVA immunized controls. To investigate the effect of IC in DC functions, naïve WT and CD16-/- BMDCs were stimulated with SEB with either OVA or OVA-IC, and DC maturation and survival were determined. Compared to SEB-OVA stimulation, SEB+OVA-IC-stimulated WT and CD16-/- BMDCs have similar maturation, but a decrease in late apoptotic cells. Our findings suggest that ICs down-regulate the allergic response in the gut of WT and CD16-/- mice leading to lower systemic responses, and yet preserves DC functions. Thus, IC might induce a regulatory network in the gut mucosal that allows sensitization, but fails to trigger an exacerbated inflammatory response.