Carbohydrate(s) that are Contained within Peanut Flour Promote Allergic Sensitization to Peanut through CARD9 Pathway

Mice develop peanut allergy when they inhale peanut flour without any exogenous adjuvants. The goal of this study was to investigate the cellular and molecular mechanisms of peanut allergen sensitization by using a mouse model and in vitro cell culture. Naïve BALB/c mice were exposed intranasally (i.n.) to peanut flour once or twice a week for up to 4 weeks. Serum levels of peanut-specific IgE and IgG isotypes were determined, and acute anaphylactic response was examined. The roles for caspase recruitment domain-containing protein 9 (CARD9), a critical adaptor protein of C-type lectin receptors, were examined by using gene-deficient mice. Chemical deglycosylation with periodic acid was used to investigate the roles for carbohydrate molecule(s) in peanut flour. Mice produced peanut-specific IgE antibody when they were exposed i.n. to peanut flour; these mice developed acute anaphylaxis when challenged intraperitoneally with peanut extract. Isolated alveolar macrophages produced IL-1α/β when stimulated with peanut flour in vitro. These in vivo and in vitro responses were significantly decreased when carbohydrates were removed from peanut flour by periodic acid treatment. CARD9-deficient mice produced less peanut-specific IgE as compared to wild-type mice. Finally, alveolar macrophages from CARD9-deficien mice produced no or little IL-1α/β when cultured with peanut flour in vitro. CARD9 are involved in development of peanut allergy in response inhaled peanut flour in mice. Carbohydrate structure(s) within peanut flour that interact with lectins in immune cells likely play a pivotal role in promoting allergen sensitization.