RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma
Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown...
| Published in: | eLife |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-01-01
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| Online Access: | https://elifesciences.org/articles/21199 |
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| author | Jaisy Arikkatt Md Ashik Ullah Kirsty Renfree Short Vivan Zhang Wan Jun Gan Zhixuan Loh Rhiannon B Werder Jennifer Simpson Peter D Sly Stuart B Mazzone Kirsten M Spann Manuel AR Ferreira John W Upham Maria B Sukkar Simon Phipps |
| author_facet | Jaisy Arikkatt Md Ashik Ullah Kirsty Renfree Short Vivan Zhang Wan Jun Gan Zhixuan Loh Rhiannon B Werder Jennifer Simpson Peter D Sly Stuart B Mazzone Kirsten M Spann Manuel AR Ferreira John W Upham Maria B Sukkar Simon Phipps |
| author_sort | Jaisy Arikkatt |
| collection | DOAJ |
| container_title | eLife |
| description | Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown. However, both respiratory syncytial virus (RSV) infection and mutations in the receptor for advanced glycation endproducts (RAGE) are risk factors for asthma development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life infection with pneumonia virus of mice (PVM; a murine analogue of RSV). The elevated viral load was associated with the release of high mobility group box-1 (HMGB1) which triggered airway smooth muscle remodelling in early-life. Re-infection with PVM in later-life induced many of the cardinal features of asthma in the absence of eosinophilic or neutrophilic inflammation. Anti-HMGB1 mitigated both early-life viral disease and asthma-like features, highlighting HMGB1 as a possible novel therapeutic target. |
| format | Article |
| id | doaj-art-e418fb7a616e4be3bd804cf4d5fedc33 |
| institution | Directory of Open Access Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2017-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| spelling | doaj-art-e418fb7a616e4be3bd804cf4d5fedc332025-08-19T21:24:56ZengeLife Sciences Publications LtdeLife2050-084X2017-01-01610.7554/eLife.21199RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthmaJaisy Arikkatt0Md Ashik Ullah1Kirsty Renfree Short2Vivan Zhang3Wan Jun Gan4Zhixuan Loh5Rhiannon B Werder6Jennifer Simpson7Peter D Sly8Stuart B Mazzone9Kirsten M Spann10Manuel AR Ferreira11John W Upham12Maria B Sukkar13Simon Phipps14https://orcid.org/0000-0002-7388-3612School of Biomedical Science, University of Queensland, Brisbane, AustraliaSchool of Biomedical Science, University of Queensland, Brisbane, Australia; Woolcock Institute of Medical Research, Sydney Medical School, University of Sydney, New South Wales, AustraliaSchool of Biomedical Science, University of Queensland, Brisbane, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, AustraliaSchool of Biomedical Science, University of Queensland, Brisbane, AustraliaSchool of Biomedical Science, University of Queensland, Brisbane, AustraliaSchool of Biomedical Science, University of Queensland, Brisbane, AustraliaSchool of Biomedical Science, University of Queensland, Brisbane, AustraliaSchool of Biomedical Science, University of Queensland, Brisbane, AustraliaAustralian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia; Centre for Children's Health Research Children's Health Queensland, The University of Queensland, Brisbane, AustraliaSchool of Biomedical Science, University of Queensland, Brisbane, AustraliaAustralian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia; School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Australia; School of Biomedical Science, Queensland University of Technology, Brisbane, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, AustraliaAustralian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia; School of Medicine, The University of Queensland, Princess Alexandra Hospital Brisbane, Brisbane, AustraliaWoolcock Institute of Medical Research, Sydney Medical School, University of Sydney, New South Wales, Australia; Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, AustraliaSchool of Biomedical Science, University of Queensland, Brisbane, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, AustraliaAsthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown. However, both respiratory syncytial virus (RSV) infection and mutations in the receptor for advanced glycation endproducts (RAGE) are risk factors for asthma development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life infection with pneumonia virus of mice (PVM; a murine analogue of RSV). The elevated viral load was associated with the release of high mobility group box-1 (HMGB1) which triggered airway smooth muscle remodelling in early-life. Re-infection with PVM in later-life induced many of the cardinal features of asthma in the absence of eosinophilic or neutrophilic inflammation. Anti-HMGB1 mitigated both early-life viral disease and asthma-like features, highlighting HMGB1 as a possible novel therapeutic target.https://elifesciences.org/articles/21199asthmapaucigranulocyticvirus infectionRAGEHMGB1 |
| spellingShingle | Jaisy Arikkatt Md Ashik Ullah Kirsty Renfree Short Vivan Zhang Wan Jun Gan Zhixuan Loh Rhiannon B Werder Jennifer Simpson Peter D Sly Stuart B Mazzone Kirsten M Spann Manuel AR Ferreira John W Upham Maria B Sukkar Simon Phipps RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma asthma paucigranulocytic virus infection RAGE HMGB1 |
| title | RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma |
| title_full | RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma |
| title_fullStr | RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma |
| title_full_unstemmed | RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma |
| title_short | RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma |
| title_sort | rage deficiency predisposes mice to virus induced paucigranulocytic asthma |
| topic | asthma paucigranulocytic virus infection RAGE HMGB1 |
| url | https://elifesciences.org/articles/21199 |
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