Unknown

Dataset Information

0

IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming.


ABSTRACT: High risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high (BN) versus low susceptibility (PVG) to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype. We also investigated potential risk mitigation via pretreatment with the immune training agent OM-85. Virus/allergen coexposure in low-risk PVG rats resulted in rapid and transient airways inflammation alongside IRF7 gene network formation. In contrast, responses in high-risk BN rats were characterized by severe airways eosinophilia and exaggerated proinflammatory responses that failed to resolve, and complete absence of IRF7 gene networks. OM-85 had more profound effects in high-risk BN rats, inducing immune-related gene expression changes in lung at baseline and reducing exaggerated airway inflammatory responses to virus/allergen coexposure. In low-risk PVG rats, OM-85 boosted IRF7 gene networks in the lung but did not alter baseline gene expression or cellular influx. Distinct IRF7-associated asthma risk immunophenotypes have dichotomous responses to virus/allergen coexposure and respond differentially to OM-85 pretreatment. Extrapolating to humans, our findings suggest that the beneficial effects OM-85 pretreatment may preferentially target those in high-risk subgroups.

SUBMITTER: de Jong E 

PROVIDER: S-EPMC8339879 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC5338315 | biostudies-literature
| S-EPMC6438742 | biostudies-literature
| S-EPMC9926922 | biostudies-literature
| S-EPMC8024857 | biostudies-literature
| S-EPMC5363804 | biostudies-literature
| S-EPMC10559651 | biostudies-literature
| S-EPMC3875422 | biostudies-literature
| S-EPMC8297025 | biostudies-literature
| S-EPMC6008049 | biostudies-literature
2024-03-11 | GSE260787 | GEO