Author Identifier

Claus T Christophersen

https://orcid.org/0000-0003-1591-5871

Document Type

Journal Article

Publication Title

Frontiers in Immunology

Publisher

Frontiers

School

School of Medical and Health Sciences / Centre for Integrative Metabolomics & Computational Biology

RAS ID

36273

Comments

de Jong, E., Lauzon-Joset, J.-F., Leffler, J., Serralha, M., Larcombe, A. N., Christophersen, C. T., . . . Bosco, A. (2021). IRF7-associated immunophenotypes have dichotomous responses to virus/allergen coexposure and OM-85-induced reprogramming. Frontiers in Immunology, 12, article 699633. https://doi.org/10.3389/fimmu.2021.699633

Abstract

High risk for virus-induced asthma exacerbations in children is associated with an IRF7loimmunophenotype, but the underlying mechanisms are unclear. Here, we applied aSystems Biology approach to an animal model comprising rat strains manifesting high(BN)versuslow susceptibility (PVG) to experimental asthma, induced by virus/allergencoexposure, to elucidate the mechanism(s)-of-action of the high-risk asthmaimmunophenotype. We also investigated potential risk mitigationviapretreatment withthe immune training agent OM-85. Virus/allergen coexposure in low-risk PVG rats resultedin rapid and transient airways inflammation alongside IRF7 gene network formation. Incontrast, responses in high-risk BN rats were characterized by severe airways eosinophiliaand exaggerated proinflammatory responses that failed to resolve, and complete absenceof IRF7 gene networks. OM-85 had more profound effects in high-risk BN rats, inducingimmune-related gene expression changes in lung at baseline and reducing exaggeratedairway inflammatory responses to virus/allergen coexposure. In low-risk PVG rats, OM-85boosted IRF7 gene networks in the lung but did not alter baseline gene expression orcellular influx. Distinct IRF7-associated asthma risk immunophenotypes havedichotomous responses to virus/allergen coexposure and respond differentially to OM-85 pretreatment. Extrapolating to humans, ourfindings suggest that the beneficial effectsOM-85 pretreatment may preferentially target those in high-risk subgroups.

DOI

10.3389/fimmu.2021.699633

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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