A Novel Murine Model of Allergic Airway Inflammation
Principal Investigator: Avery August
Co-PI: Weishan Huang
DESCRIPTION (provided by applicant):
Allergic asthma affects almost 300 million people worldwide, with up to 11% of the population of the United States alone and its rate continues to increase in urbanized countries. This disease cannot be cured, making it one of the most expensive diseases for healthcare systems in developed countries. A better understanding of this disease will allow the development of better and more effective treatments, however, we still lack a complete understanding of the mechanisms leading to and that maintain the disease. Much work has been done using mouse models of allergic airway disease, which has led to a deeper understanding of this disease. However, there are still a number of caveats to the use of mouse models to understand the immune mechanisms behind allergic asthma, including the genetics of inbred mouse strains, differences between mouse and human immune systems, and the increasing appreciation of the role of the microbiome in shaping this response. This is because laboratory mice are normally kept in very clean specific pathogen free conditions (SPF), which has been recently shown to alter development of the immune system. By contrast, humans are obviously not in SPF conditions, being naturally exposed to normal microbial loads in their usual lives. This makes this work highly significant. Our recent data indicates that exposing mice to a broad microbial load makes the phenotype of their immune systems more “human-like", affecting their response to HDM induced allergic airway inflammation. Based on our results, we have developed the hypothesis that “normalizing” the microbiome of- mice alters the development of the immune system to make their phenotypes more “human-like”, and will alter its response to HDM induced allergic airway inflammation. We propose experiments in two specific aims that will determine the effect of broad microbial exposure on the development of allergic asthma in response to HDM exposure in mice and compare immune cells that develop in response to HDM exposure in SPF and PSE mice to those from humans with HDM allergic asthma. This work is extremely innovative as we utilize novel and unique approaches, and have exciting preliminary data that when fleshed out, will provide information on whether this represents a novel approach to studying allergic lung inflammation, and could inform other murine models of human disease.