Deficient inflammasome activation permits an exaggerated asthma phenotype in rhinovirus C-infected immature mice
dc.contributor.author | Han, M | |
dc.contributor.author | Ishikawa, T | |
dc.contributor.author | Stroupe, CC | |
dc.contributor.author | Breckenridge, HA | |
dc.contributor.author | Bentley, JK | |
dc.contributor.author | Hershenson, MB | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-02-01T17:47:44Z | |
dc.date.available | 2023-02-01T17:47:44Z | |
dc.date.issued | 2021-11-01 | |
dc.identifier.issn | 1933-0219 | |
dc.identifier.issn | 1935-3456 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/34354243 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/175724 | en |
dc.description.abstract | Compared to other RV species, RV-C has been associated with more severe respiratory illness and is more likely to occur in children with a history of asthma or who develop asthma. We therefore inoculated 6-day-old mice with sham, RV-A1B, or RV-C15. Inflammasome priming and activation were assessed, and selected mice treated with recombinant IL-1β. Compared to RV-A1B infection, RV-C15 infection induced an exaggerated asthma phenotype, with increased mRNA expression of Il5, Il13, Il25, Il33, Muc5ac, Muc5b, and Clca1; increased lung lineage-negative CD25+CD127+ST2+ ILC2s; increased mucous metaplasia; and increased airway responsiveness. Lung vRNA, induction of pro-inflammatory type 1 cytokines, and inflammasome priming (pro-IL-1β and NLRP3) were not different between the two viruses. However, inflammasome activation (mature IL-1β and caspase-1 p12) was reduced in RV-C15-infected mice compared to RV-A1B-infected mice. A similar deficiency was found in cultured macrophages. Finally, IL-1β treatment decreased RV-C-induced type 2 cytokine and mucus-related gene expression, ILC2s, mucous metaplasia, and airway responsiveness but not lung vRNA level. We conclude that RV-C induces an enhanced asthma phenotype in immature mice. Compared to RV-A, RV-C-induced macrophage inflammasome activation and IL-1β are deficient, permitting exaggerated type 2 inflammation and mucous metaplasia. | |
dc.format.medium | Print-Electronic | |
dc.language | eng | |
dc.publisher | Elsevier | |
dc.rights | Licence for published version: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | Animals | |
dc.subject | Asthma | |
dc.subject | Biomarkers | |
dc.subject | Cell Line | |
dc.subject | Coxsackievirus Infections | |
dc.subject | Cytokines | |
dc.subject | Disease Models, Animal | |
dc.subject | Disease Progression | |
dc.subject | Disease Susceptibility | |
dc.subject | Enterovirus | |
dc.subject | Humans | |
dc.subject | Immunity, Innate | |
dc.subject | Immunophenotyping | |
dc.subject | Inflammasomes | |
dc.subject | Lymphocyte Activation | |
dc.subject | Lymphocyte Subsets | |
dc.subject | Macrophages | |
dc.subject | Mice | |
dc.subject | Phenotype | |
dc.title | Deficient inflammasome activation permits an exaggerated asthma phenotype in rhinovirus C-infected immature mice | |
dc.type | Article | |
dc.identifier.pmid | 34354243 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/175724/2/Deficient inflammasome activation permits an exaggerated asthma phenotype in rhinovirus C-infected immature mice.pdf | |
dc.identifier.doi | 10.1038/s41385-021-00436-0 | |
dc.identifier.doi | https://dx.doi.org/10.7302/6938 | |
dc.identifier.source | Mucosal Immunology | |
dc.description.version | Published version | |
dc.date.updated | 2023-02-01T17:47:41Z | |
dc.identifier.orcid | 0000-0001-8865-7979 | |
dc.identifier.orcid | 0000-0001-9436-5593 | |
dc.identifier.volume | 14 | |
dc.identifier.issue | 6 | |
dc.identifier.startpage | 1369 | |
dc.identifier.endpage | 1380 | |
dc.identifier.name-orcid | Han, M | |
dc.identifier.name-orcid | Ishikawa, T | |
dc.identifier.name-orcid | Stroupe, CC | |
dc.identifier.name-orcid | Breckenridge, HA | |
dc.identifier.name-orcid | Bentley, JK; 0000-0001-8865-7979 | |
dc.identifier.name-orcid | Hershenson, MB; 0000-0001-9436-5593 | |
dc.working.doi | 10.7302/6938 | en |
dc.owningcollname | Pediatrics and Communicable Diseases, Department of |
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