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Airway administration of OM-85, a bacterial lysate, blocks experimental asthma by targeting dendritic cells and the epithelium/IL-33/ILC2 axis
Journal article   Peer reviewed

Airway administration of OM-85, a bacterial lysate, blocks experimental asthma by targeting dendritic cells and the epithelium/IL-33/ILC2 axis

Vadim Pivniouk, Joao A. Gimenes-Junior, Peace Ezeh, Ashley Michael, Oksana Pivniouk, Seongmin Hahn, Sydney R. VanLinden, Sean P. Malone, Amir Abidov, Dayna Anderson, …
Journal of allergy and clinical immunology, Vol.149(3), pp.943-956
03/01/2022
DOI: 10.1016/j.jaci.2021.09.013
PMCID: PMC8901455
PMID: 34560105

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Abstract

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 intranasal administration of microbial products from farm environments abrogates experimental allergic asthma. We sought 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. Different strains of mice sensitized and challenged with ovalbumin or Alternaria received OM-85 intranasally, 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. 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. 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 intranasal OM-85 administration may reflect its direct access to the airway mucosal networks controlling the initiation and development of allergic asthma. [Display omitted]
 Asthma adaptive immunity airway compartment allergic inflammation Bacterial lysate innate immunity intranasal route microbial interventions OM-85

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