Control of Lung Inflammation by Microbiome and Peptidoglycan Recognition Protein
Abstract
This project proposes to identify new predisposing factors for asthma and lung inflammation, and thus is related to the Respiratory Health and the Acute Lung Injury Fiscal Year 2015 Peer Reviewed Medical Research Program topics, and especially to "acute eosinophilic pneumonia, constrictive bronchiolitis, asthma, allergies, and other chronic lung diseases." Asthma is one of the most frequent and most severe of allergic and inflammatory diseases. It affects 7% of the US population and its annual healthcare costs exceed $20 billion. The prevalence of asthma has been sharply increasing in the last several decades. This increase in the prevalence of asthma affects the military in three ways. First, this trend progressively limits the numbers of able-body eligible recruits qualified to serve in the military because the military has exclusion criteria for asthma. Second, this increase affects military families and Veterans, which is a growing burden on the military healthcare system and on military families in general. Third, new-onset asthma is diagnosed in deployed Soldiers with increasing frequency, approaching the frequency in general population, despite asthma being an exclusion criterion for military enlistment. This high risk of newly diagnosed asthma in deployed US Soldiers is alarming, considering the asthma-free personnel at the start of their service. Various respiratory hazards in the deployed environment, including dust, toxic smoke from burn pits, exhaust emissions, roadside and car bombs, and respiratory allergens, such as molds, further amplify the risk for Soldiers of developing asthma and other inflammatory lung diseases. Prevention of asthma is based on avoidance of allergens and the use of anti-inflammatory medications, whereas treatment of acute symptoms is usually accomplished by using short-acting inhalers. These treatments have been used for decades, but only with partial success because they fail to fully control all cases of asthma, because they do not offer a cure, but only symptomatic relief, and because they failed to prevent this increase in the prevalence of asthma. Thus, new approaches to the prevention and treatment of asthma are needed. However, to develop such new prevention and treatment methods, better understanding of the causes of asthma and what controls the development of asthma is needed. The most effective long-term approach to diminishing the prevalence of asthma would be to reverse the trend of increasing prevalence by eliminating its causes, which would reduce asthma prevalence to the low numbers seen decades ago. However, this cannot be currently accomplished because the causes of this increased prevalence are unknown. The novel idea that will be explored in this proposal is the possibility that one of the causes for the increasing prevalence of asthma are the changes in the types of bacteria that are normally present on the body, especially in the respiratory tract and in the intestinal tract (collectively called microbiome). These bacteria usually have beneficial effects for their host, but under some conditions beneficial bacteria may be lost and replaced with harmful bacteria that predispose the host to diseases. We propose in this project that such a change from beneficial to harmful bacteria increases the sensitivity to asthma. We further propose that one of the components of the host immune system, a protein with antibacterial activity called Peptidoglycan Recognition Protein 1 (Pglyrp1), controls the composition of these bacteria, and the presence or absence of the Pglyrp1 protein results in the dominance of harmful or beneficial bacteria in the microbiome. Thus, this project will test the hypothesis that Pglyrp1-controlled bacteria in the respiratory and/or intestinal microbiomes affect the sensitivity to asthma and lung and airways inflammation. The positive impact of this project will be proving this novel concept of the control of the sensit
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610230
Entities
People
- Roman Dziarski
Organizations
- Indiana University – Purdue University Indianapolis
- United States Army