Allergic asthma is common in Westernized countries and its prevalence has increased greatly during the last century. Interestingly, recent research has shown that exposure to pets during infancy correlates with a lower risk of developing allergy and asthma in later life. In addition, data generated by the PPG investigators have demonstrated that pets can be associated with alterations to the microbiota in house dust. It is well known that soil and dust are ingested by children, and alterations in gut microbiome have been associated with risk for allergic asthma development. In order to further our understanding of the mechanisms that lead to the alterations observed clinically, this project has established and utilized models of pulmonary disease with exposure to dust from homes with dogs versus no pets. Using two different mouse models of allergic asthma (cockroach antigen and ovalbumin), we will study pulmonary immune responses after oral exposure to house dust using samples collected from homes with dogs and without pets. We will test the overall hypothesis that the composition of the dust microbiome from homes with dogs versus no pets differentially alters pulmonary immune responses during allergen exposure by changing the Gl microbiota or bacterial community composition (BCC), resulting in systemic changes in antigen presenting cell and bone marrow progenitor cell programming and allergic outcomes. To test this hypothesis, we will specifically focus on clinically relevant mechanisms involved in the ability of pulmonary-derived allergen responses to induce Th2 cytokines, mucus hypersecretion, physiologic changes (AHR), and changes in innate responses locally as well as systemically. Our studies will: 1) establish that exposure of mice to dust from homes with dogs versus no pets will result in differential changes in the Gl BCC, 2) demonstrate that the dog dust-altered gut microbiome alters pulmonary allergic responses, 3) establish that the dog dust-induced changes alter dendritic cell responses in the lung, 4) identify that changes in innate responses are a systemic effect by examining bone marrow cell responses, and 5) utilize innovative mouse models to derive the cellular mechanisms of the altered responses. BCC will be measured using the G3 PhyloChip. Thus, these studies, in close collaboration with the other projects in this PPG, will clarify a number of previously unexplored questions and will guide exploration into this novel area of research.

Public Health Relevance

Asthma is one of the most common ailments that affects Americans of all ages. The treatment of asthma has not changed significantly and the prevalence of asthma continues to increase. A better understanding of how asthma develops and the ability to identify prevention strategies for use in early life is imperative. These studies will explore mechanisms associated with the household environment linked to pets and asthma using a clinically relevant animal model of airways disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI089473-03
Application #
8843146
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Henry Ford Health System
Department
Type
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
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