Environmental conditions and their impact on host immunity

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DESCRIPTION (provided by applicant): Industrialized countries have experienced an increase in Th2-dependent, IgE- mediated allergic diseases such as food allergy, asthma, and hay fever. Food allergy causes 30,000 cases of anaphylaxis and 200 deaths annually in the United States alone. The cause for the escalation in allergic disease remains unknown. In recent decades, potential risk factors such as improved living conditions and the use of aluminum (alum)-adjuvanted vaccines have been proposed as being associated with the increased prevalence of allergic disease. It is our hypothesis that the cumulative effect of the allergy risk factors creates a Th2-biased immune environment in the host that predisposes the host to the development of allergy. The goal of this proposal is to utilize a mouse model to determine if the presence of proposed allergy risk factors including low LPS environment and exposure to alum-adjuvanted vaccines influences the phenotype of the host systemic and mucosal immune system. Additionally, we will determine if the presence of these allergy risk factors influences the development of allergic sensitization to peanut. To achieve this goal, mice will be maintained in standard mouse housing conditions or in conditions designed to mimic modern, industrialized countries that have experienced increased allergic diseases. The "modern" conditions will include low endotoxin, exposure to alum-adjuvanted immunizations or low endotoxin combined with alum-adjuvanted vaccines. All mice will be sensitized to peanut antigens. Upon completion of sensitization mice will be challenged with peanut and monitored for the incidence and severity of an allergic reaction. The experiments proposed in this application will provide the foundation for future mechanistic studies to define environmental factors that contribute to the increased prevalence of food allergy and provide a model to evaluate novel therapies for their ability to prevent the induction of peanut food allergy.