Pertussis adjuvant prolongs intestinal hypersensitivity

Background: Immediate hypersensitivity reactions are a hallmark of allergic disease, and result in the clinical features of food allergy, hayfever, and atopic asthma. The mechanism by which an individual becomes sensitized to an ingested or airborne allergen is not clear, however exposure to bacteria or bacterial products that act as adjuvants may be a contributing factor. The purpose of this study was to examine the role of pertussis toxin (PT) in inducing intestinal hypersensitivity reactions, particularly the ability of the adjuvant to prolong the sensitization. Methods: Rats were sensitized to ovalbumin (OA) by injection of OA alone or with 50 ng PT. Secretory responses to OA challenge and nerve stimulation were assessed in jejunal tissues mounted in Ussing chambers. Results: Jejunal segments from rats sensitized to OA alone responded to antigen challenge with ion secretion, but sensitization was transient in that specific IgE titers and responses to luminal antigen disappeared by 14 days. In contrast, co-administration of 50 ng PT with OA resulted in long-tasting sensitization. Secretory responses to both luminal and serosal OA challenge were present 8 months after primary immunization. Enhanced secretory responses to nerve stimulation, increased mucosal mast cell numbers, as well as elevated IgE titers were also induced and may have contributed to the overall responsiveness of the intestine to antigen challenge. Conclusions: Our findings indicate nanogram quantities of PT, when administered with a food protein, result in long-term sensitization to the antigen, and altered intestinal neuroimmune function. These data suggest that exposure to bacterial pathogens may prolong the normally transient immune responsiveness to inert food antigens.