Airway Microbiota-Host Interactions Regulate Secretory Leukocyte Protease Inhibitor Levels and Influence Allergic Airway Inflammation

Homeostatic mucosal immune responses are fine-tuned by naturally evolved interactions with native microbes, and integrating these relationships into experimental models can provide new insights into human diseases. Here, we leverage a murine-adapted airway microbe, Bordetella pseudohinzii (Bph), to investigate how chronic colonization impacts mucosal immunity and the development of allergic airway inflammation (AAI). Colonization with Bph induces the differentiation of interleukin-17A (IL-17A)-secreting T-helper cells that aid in controlling bacterial abundance. Bph colonization protects from AAI and is associated with increased production of secretory leukocyte protease inhibitor (SLPI), an antimicrobial peptide with anti-inflammatory properties. These findings are additionally supported by clinical data showing that higher levels of upper respiratory SLPI correlate both with greater asthma control and the presence of Haemophilus, a bacterial genus associated with AAI. We propose that SLPI could be used as a biomarker of beneficial host-commensal relationships in the airway. [Display omitted] •Bordetella pseudohinzii (Bph) colonizes the mouse airway and induces a Th17 response•Bph-colonized mice show reduced allergic airway inflammation (AAI) in an asthma model•The antimicrobial peptide SLPI is linked to diminished AAI and is regulated by IL-17A•In humans, upper airway microbiota composition was correlated with SLPI abundance Asthma is known to be modified by airway microbes. Jaeger et al. use a murine-adapted bacterium to show that airway colonization evokes a Th17 response associated with increased SLPI, an antimicrobial peptide, and protection from lung inflammation. In people, SLPI was correlated with airway microbiota composition.