Reduced severity of peanut-induced anaphylaxis in TLR9-deficient mice is associated with selective defects in humoral immunity

Signaling through the innate immune system can promote or suppress allergic sensitization. TLR9 has modulatory effects on the mucosal immune system, and we hypothesized that TLR9 would influence susceptibility to allergic sensitization to foods. We observed that TLR9−/− mice were resistant to peanut-induced anaphylaxis. This was associated with a significant impairment in total IgE and peanut-specific IgE and IgA, but not IgG1 or Th2 cytokine production. TLR9−/− mice had reduced development of Peyer’s patches, but resistance to sensitization was not restricted to oral routes. Rag1-deficient mice were reconstituted with TLR9+/+ or −/− B cells plus CD4+ T cells. TLR9−/− B cells regained the ability to produce IgE in the presence of a wild-type environment. Our results demonstrate that TLR9 on an unknown cell type is required for the development of IgE-producing B cells, and we conclude that TLR9 signaling indirectly shapes the immune response for optimal IgE production.