Airway Microbes modulate Allergic Airway Inflammation through Secreted Leukocyte Proteinase Inhibitor

Changes in the airway microbiota are associated with the development of immuno-inflammatory diseases within the respiratory tract, but the mechanisms underlying this observation are incompletely understood. Here, we use 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) in an ovalbumin model of asthma. Airway colonization of mice with Bph induced the differentiation of bacterial antigen-specific Th17 cells that aid in controlling bacterial colonization. Mice colonized with Bph were additionally protected from an ovalbumin model of AAI, experiencing reduced eosinophilic infiltration, goblet cell metaplasia, transcription of Th2 cytokines, and airway hyperresponsiveness compared to noncolonized control mice. Whole lung tissue transcriptional profiling identified Secreted Leukocyte Proteinase Inhibitor (SLPI), an antimicrobial peptide with established anti-allergy properties, as a potential airway microbiota modulated factor that protects from AAI. Lung SLPI expression is enhanced by Bph colonization and supports a model by which Bph protects from AAI through the upregulation of SLPI within the airway. Comparison of SLPI abundances and 16S rRNA data from human airway samples demonstrated that microbial composition accounts for over 50% of the variance in SLPI abundance across a population of healthy adults and children. Together, these findings show that SLPI abundance in the airway is closely associated with the airway microbiota and may help to mediate the effect of the airway microbiota on AAI.