Role of the indoor exposome in peanut allergy development

ABSTRACT There is growing evidence that early-life environmental exposures are contributing to the increasing prevalence of allergic diseases including food allergy. Food allergy rates, particularly for peanut, have increased dramatically in industrialized countries over the last few decades, suggesting environmental factors are driving the epidemic. Recent studies show that inhalational or cutaneous exposure to peanut within the home may be a risk factor for peanut allergy. In addition to food antigens, the indoor exposome also includes immunostimulatory agents, such as microbial products and air pollutants, which can act as adjuvants and promote allergic sensitization to antigens. Whether exposure to environmental adjuvants influences peanut allergy development is unclear. We have developed a novel mouse model that mimics inhalational exposure to environmental peanut within the home. We have found that co-exposure to inhaled peanut and indoor dust, which contains environmental adjuvants to which children are exposed, induced allergic sensitization and the development of peanut allergy in mice. Moreover, we have found that co-exposure to inhaled peanut and air pollutants, including diesel exhaust particles and particulate matter, also induced peanut allergy in our animal model. In this proposal, we will determine if exposure to environmental adjuvants in indoor dust is associated with peanut sensitization in infants, and also investigate the mechanisms by which environmental adjuvants (e.g., indoor dust, air pollutants) promote peanut allergy development. In Aim 1, we will use an airway sensitization animal model and primary human bronchial epithelial cell culture system to compare the adjuvant activity of indoor dust samples collected from the homes of peanut- sensitized and nonsensitized infants, and determine if adjuvant activity is associated with peanut sensitization status. In Aim 2, we will use animal models to define the innate immune signaling pathways required for indoor dust-mediated airway sensitization to peanut. In Aim 3, we will investigate the immunological mechanisms by which inhaled air pollutants promote peanut allergy development in our animal model. These studies will greatly expand our understanding of how the indoor exposome influences food allergy development and help direct future environmental interventions aimed at preventing peanut allergy in children.