Airway Microbiota-Host Interactions Regulate Secreted Leukocyte Proteinase Inhibitor Levels and Influence Allergic Airway Inflammation

Mucosal immune responses fine-tuned by naturally evolved interactions with native microbes influence airway inflammation but are not routinely integrated into experimental models. Here, we leverage a recently discovered murine-adapted airway microbe, Bordetella pseudohinzii (Bph), to investigate how chronic colonization impacts mucosal immunity and the development of allergic airway inflammation (AAI). Despite the persistent colonization, we did not observe significant weight loss in Bph colonized mice. Microscopic examination of the lungs demonstrated the formation of lymphoid aggregates, consistent with inducible Bronchus Associated Lymphoid Tissue (iBALT). Airway colonization of mice with Bph elicits an antigen-specific Th17 immune response that aids in controlling bacterial abundance. Remarkably, when animals undergo allergic airway challenge, mice previously colonized with Bph demonstrate protection from AAI. This phenotype corresponded to a reduction in type 2 cytokines, eosinophilic infiltration, goblet cell metaplasia, and airway hyper responsiveness. Colonization with Bph does not appear to impact the degree of allergic sensitization nor the presentation of allergen in the lung. Further, colonization and the Th17 response was associated with increased expression of Secreted Leukocyte Proteinase Inhibitor (SLPI), an antimicrobial peptide with anti-inflammatory properties. We confirmed these findings in humans by showing that higher levels of SLPI correlate both to improved asthma control and the presence of the asthma-associated bacterium, Haemophilus influenzae. We propose that SLPI could be used as a biomarker of beneficial host-commensal relationships in the airway.