Corticosteroid effects on bacterial behaviors in the respiratory tract

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

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Abstract

Project Summary/Abstract Inhaled corticosteroids (ICSs) are widely prescribed for the treatment of asthma and chronic obstructive pulmonary disease (COPD). However, not all patients respond to ICSs and their long-term use is associated with adverse outcomes. The potential for inappropriate or excessive treatment with ICSs is also a concern, given challenges in identifying patients most likely to benefit. The effects of corticosteroids on host immune responses at the cellular and molecular level have been well studied. In contrast, very few investigations have considered, much less examined, if inhaled corticosteroids can directly affect the behavior of bacteria that are part of the respiratory microbiota and modulate bacterial fitness, survival, or even virulence. Of particular interest are potentially pathogenic members of the Proteobacteria, shown in recent studies to be enriched in the lower airways of asthmatic and COPD patients with more advanced disease, when treatment with ICS is also more common. This project will explore if ICSs can directly modulate the behavior of potentially pathogenic members of the airway microbiota, and in turn alter the level of immune responses elicited by `CS-conditioned' bacteria from airway epithelial cells, compared to non-CS-conditioned bacteria. We will couple in vitro culture exposure models with meta-transcriptomic (RNA-seq) studies, to examine the impact of bacterial-ICS interactions on both species phenotype and responses elicited by CS-conditioned species from epithelial cells. This work will build upon evidence from recent translation-oriented clinical studies to advance understanding of the functional consequences of airway microbial dysbiosis seen in asthmatic and COPD patients.