Testing the susceptibility of mice with normal microbial experience to induction of allergic airway disease

Abstract

Abstract Allergic asthma is a large and growing medical problem in the developed world. The hygiene hypothesis posits that improved sanitation, vaccination programs, and increased antibiotic use have limited our exposure to natural infections, leading to immune systems that are more vulnerable to pathological responses. It has been difficult to test whether these advancements in public health can explain some of the increased incidence in allergic asthma, partly because laboratory mice commonly used in research are housed in a clean and highly controlled environment (known as specific pathogen free, or SPF). Cohousing SPF laboratory mice with mice from pet stores leads to acquisition of natural mouse pathogens through physiological animal-to-animal transmission. Our research group has demonstrated that this normal microbial experience dramatically alters the immune system, making it more similar to the immune system of adult humans. We used this “dirty” cohousing mouse model to test the effect of physiological microbial exposure on susceptibility to allergic airway disease. SPF and cohoused mice were sensitized and challenged intranasally with house dust mite (HDM) extract. Exposure to HDM induced eosinophilic airway inflammation and immune cell infiltration in SPF mice that resembles airway pathology of asthmatic patients. Serum levels of IgE and IgG1 antibodies to HDM were also elevated. Immune cell populations infiltrating the lung and activation of antigen-specific CD4+ T cells were also analyzed. We are currently investigating the immune response to this allergen exposure model in cohoused mice. Results from these studies will help explain the impact of environmental and microbial experience on susceptibility to allergic asthma.