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

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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 of Allergy and Clinical Immunology ( IF 11.4 ) Pub Date : 2021-09-22 , DOI: 10.1016/j.jaci.2021.09.013
Vadim Pivniouk ₁ , Joao A Gimenes-Junior ₂ , Peace Ezeh ₂ , Ashley Michael ₂ , Oksana Pivniouk ₂ , Seongmin Hahn ₂ , Sydney R VanLinden ₂ , Sean P Malone ₂ , Amir Abidov ₃ , Dayna Anderson ₂ , Justyna Gozdz ₂ , Avery DeVries ₄ , Fernando D Martinez ₄ , Christian Pasquali ₅ , Donata Vercelli ₆

Affiliation

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 intranasal administration of microbial products from farm environments abrogates experimental allergic asthma.

Objectives

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.

Methods

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.

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.

Conclusions

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.

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