Airway Microbiota-Host Interactions Regulate Secreted Leukocyte Proteinase 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 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). Colonization with Bph induced the differentiation of IL-17A secreting T-helper cells that aid in controlling bacterial abundance. Bph colonization protected from AAI and was associated with increased Secreted Leukocyte Proteinase Inhibitor (SLPI), an antimicrobial peptide with anti-inflammatory properties. These findings were additionally supported by clinical data showing that higher levels of upper respiratory SLPI correlate both to improved asthma control and the presence of Haemophilus, a bacterial genus associated with allergic airway inflammation. We propose that SLPI could be used as a biomarker of beneficial host-commensal relationships in the airway.