IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming
MetadataShow full item record
Funding and Sponsorship
© 2021 The Authors. Published in Frontiers in Immunology
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.
Showing items related by title, author, creator and subject.
Anti-bacterial IgE in the antibody responses of house dust mite allergic children convalescent from asthma exacerbationHales, B.; Martin, A.; Pearce, L.; Rueter, K.; Zhang, Guicheng; Khoo, S.; Hayden, C.; Bizzintino, J.; McMinn, P.; Geelhoed, G.; Lee, W.; Goldblatt, J.; Laing, I.; Lesouëf, P.; Thomas, W. (2009)Background Atopic sensitization to the house dust mite (HDM) is associated with altered antibody responses to the nasopharyngeal colonizing bacterium Haemophilus influenzae and children admitted to the emergency department ...
Rumchev, Krassi (2001)Asthma is a common chronic disorder in Western countries and is increasing in prevalence in both children and adults. Although genetic risk for atopy is an important factor for the development of asthma, it does not explain ...
Association between respiratory syncytial viral disease and the subsequent risk of the first episode of severe asthma in different subgroups of high-risk Australian children: a whole-of-population-based cohort studyHomaira, N.; Briggs, N.; Pardy, C.; Hanly, M.; Oei, J.; Hilder, L.; Bajuk, B.; Lui, K.; Rawlinson, W.; Snelling, Thomas; Jaffe, A. (2017)Objective: To determine the contribution of respiratory syncytial virus (RSV) to the subsequent development of severe asthma in different subgroups of children at risk of severe RSV disease. Settings: The study was conducted ...