BACKGROUND: Microbial interventions against allergic asthma have robust epidemiologic underpinnings and the potential to recalibrate disease-inducing immune responses. Oral administration of OM-85, a standardized lysate of human airways bacteria, is widely used empirically to prevent respiratory infections and a clinical trial is testing its ability to prevent asthma in high-risk children. We previously showed that intra-nasal administration of microbial products from farm environments abrogates experimental allergic asthma.
OBJECTIVES: To investigate whether direct administration of OM-85 to the airway compartment protects against experimental allergic asthma, and to identify protective cellular and molecular mechanisms activated through this natural route.
METHODS: Different strains of mice sensitized and challenged with Ovalbumin or Alternaria received OM-85 intra-nasally, and cardinal cellular and molecular asthma phenotypes were measured. Airway transfer experiments assessed whether OM-85-treated dendritic cells protect allergen-sensitized, OM-85-naive mice against asthma.
RESULTS: Airway OM-85 administration suppressed allergic asthma in all models acting on multiple innate and adaptive immune targets: the airway epithelium/IL-33/ILC2 axis, lung allergen-induced type-2 responses, and dendritic cells whose Myd88/Trif-dependent tolerogenic reprogramming was sufficient to transfer OM-85-induced asthma protection.
CONCLUSION: We provide the first demonstration that administering a standardized bacterial lysate to the airway compartment protects from experimental allergic asthma by engaging multiple immune pathways. Because protection required a cumulative dose 27 to 46-fold lower than the one reportedly active through the oral route, the efficacy of intra-nasal OM-85 administration may reflect its direct access to the airway mucosal networks controlling the initiation and development of allergic asthma.