IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming
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 experim...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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FRONTIERS MEDIA SA
2021
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| Subjects: | |
| Online Access: | http://purl.org/au-research/grants/nhmrc/1129996 http://hdl.handle.net/20.500.11937/86510 |
| _version_ | 1848764841384214528 |
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| author | de Jong, E. Lauzon-Joset, J.F. Leffler, J. Serralha, M. Larcombe, Alexander Christophersen, Claus Holt, P.G. Strickland, D.H. Bosco, A. |
| author_facet | de Jong, E. Lauzon-Joset, J.F. Leffler, J. Serralha, M. Larcombe, Alexander Christophersen, Claus Holt, P.G. Strickland, D.H. Bosco, A. |
| author_sort | de Jong, E. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T11:25:46Z |
| format | Journal Article |
| id | curtin-20.500.11937-86510 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:25:46Z |
| publishDate | 2021 |
| publisher | FRONTIERS MEDIA SA |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-865102021-11-30T05:36:04Z IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming de Jong, E. Lauzon-Joset, J.F. Leffler, J. Serralha, M. Larcombe, Alexander Christophersen, Claus Holt, P.G. Strickland, D.H. Bosco, A. Science & Technology Life Sciences & Biomedicine Immunology asthma exacerbation rhinovirus allergen immunomodulation IRF7 systems biology GROWTH-FACTOR-BETA ASTHMA EXACERBATIONS ADHESION MOLECULES IMMUNE-RESPONSES DENDRITIC CELLS RISK SUSCEPTIBILITY INFECTION SEVERITY ATOPY 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. 2021 Journal Article http://hdl.handle.net/20.500.11937/86510 10.3389/fimmu.2021.699633 English http://purl.org/au-research/grants/nhmrc/1129996 http://creativecommons.org/licenses/by/4.0/ FRONTIERS MEDIA SA fulltext |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Immunology asthma exacerbation rhinovirus allergen immunomodulation IRF7 systems biology GROWTH-FACTOR-BETA ASTHMA EXACERBATIONS ADHESION MOLECULES IMMUNE-RESPONSES DENDRITIC CELLS RISK SUSCEPTIBILITY INFECTION SEVERITY ATOPY de Jong, E. Lauzon-Joset, J.F. Leffler, J. Serralha, M. Larcombe, Alexander Christophersen, Claus Holt, P.G. Strickland, D.H. Bosco, A. IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming |
| title | IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming |
| title_full | IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming |
| title_fullStr | IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming |
| title_full_unstemmed | IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming |
| title_short | IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming |
| title_sort | irf7-associated immunophenotypes have dichotomous responses to virus/allergen coexposure and om-85-induced reprogramming |
| topic | Science & Technology Life Sciences & Biomedicine Immunology asthma exacerbation rhinovirus allergen immunomodulation IRF7 systems biology GROWTH-FACTOR-BETA ASTHMA EXACERBATIONS ADHESION MOLECULES IMMUNE-RESPONSES DENDRITIC CELLS RISK SUSCEPTIBILITY INFECTION SEVERITY ATOPY |
| url | http://purl.org/au-research/grants/nhmrc/1129996 http://hdl.handle.net/20.500.11937/86510 |