Inflammasome Activation is Required for Human Rhinovirus-Induced Airway Inflammation in Naïve and Allergen-Sensitized Mice.
dc.contributor.author | Han, M | |
dc.contributor.author | Bentley, JK | |
dc.contributor.author | Rajput, C | |
dc.contributor.author | Lei, J | |
dc.contributor.author | Ishikawa, T | |
dc.contributor.author | Jarman, CR | |
dc.contributor.author | Lee, J | |
dc.contributor.author | Goldsmith, AM | |
dc.contributor.author | Jackson, WT | |
dc.contributor.author | Hoenerhoff, MJ | |
dc.contributor.author | Lewis, TC | |
dc.contributor.author | Hershenson, MB | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2024-01-18T19:05:59Z | |
dc.date.available | 2024-01-18T19:05:59Z | |
dc.date.issued | 2019-05-15 | |
dc.identifier.issn | 1933-0219 | |
dc.identifier.issn | 1935-3456 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/31089187 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/192080 | en |
dc.description.abstract | Activation of the inflammasome is a key function of the innate immune response that regulates inflammation in response to microbial substances. Inflammasome activation by human rhinovirus (RV), a major cause of asthma exacerbations, has not been well studied. We examined whether RV induces inflammasome activation in vivo, molecular mechanisms underlying RV-stimulated inflammasome priming and activation, and the contribution of inflammasome activation to RV-induced airway inflammation and exacerbation. RV infection triggered lung mRNA and protein expression of pro-IL-1β and NLRP3, indicative of inflammasome priming, as well as cleavage of caspase-1 and pro-IL-1β, completing inflammasome activation. Immunofluorescence staining showed IL-1β in lung macrophages. Depletion with clodronate liposomes and adoptive transfer experiments showed macrophages to be required and sufficient for RV-induced inflammasome activation. TLR2 was required for RV-induced inflammasome priming in vivo. UV irradiation blocked inflammasome activation and RV genome was sufficient for inflammasome activation in primed cells. Naive and house dust mite-treated NLRP3−/− and IL-1β−/− mice, as well as IL-1 receptor antagonist-treated mice, showed attenuated airway inflammation and responsiveness following RV infection. We conclude that RV-induced inflammasome activation is required for maximal airway inflammation and hyperresponsiveness in naive and allergic mice. The inflammasome represents a molecular target for RV-induced asthma exacerbations. | |
dc.format.medium | Print-Electronic | |
dc.language | eng | |
dc.publisher | Elsevier | |
dc.subject | Allergens | |
dc.subject | Animals | |
dc.subject | Disease Models, Animal | |
dc.subject | Humans | |
dc.subject | Immunization | |
dc.subject | Inflammasomes | |
dc.subject | Interleukin-1beta | |
dc.subject | Mice | |
dc.subject | NLR Family, Pyrin Domain-Containing 3 Protein | |
dc.subject | Picornaviridae Infections | |
dc.subject | Pyroglyphidae | |
dc.subject | Respiratory Tract Infections | |
dc.subject | Rhinovirus | |
dc.subject | Toll-Like Receptor 2 | |
dc.title | Inflammasome Activation is Required for Human Rhinovirus-Induced Airway Inflammation in Naïve and Allergen-Sensitized Mice. | |
dc.type | Article | |
dc.identifier.pmid | 31089187 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/192080/2/1-s2.0-S1933021922002744-main.pdf | |
dc.identifier.doi | 10.1038/s41385-019-0172-2 | |
dc.identifier.doi | https://dx.doi.org/10.7302/22080 | |
dc.identifier.source | Mucosal Immunol. | |
dc.description.version | Published version | |
dc.date.updated | 2024-01-18T19:05:58Z | |
dc.identifier.orcid | 0000-0001-8865-7979 | |
dc.identifier.orcid | 0000-0001-9436-5593 | |
dc.description.filedescription | Description of 1-s2.0-S1933021922002744-main.pdf : Published version | |
dc.identifier.volume | 12 | |
dc.identifier.issue | 4 | |
dc.identifier.startpage | 958 | |
dc.identifier.endpage | 968 | |
dc.identifier.name-orcid | Han, M | |
dc.identifier.name-orcid | Bentley, JK; 0000-0001-8865-7979 | |
dc.identifier.name-orcid | Rajput, C | |
dc.identifier.name-orcid | Lei, J | |
dc.identifier.name-orcid | Ishikawa, T | |
dc.identifier.name-orcid | Jarman, CR | |
dc.identifier.name-orcid | Lee, J | |
dc.identifier.name-orcid | Goldsmith, AM | |
dc.identifier.name-orcid | Jackson, WT | |
dc.identifier.name-orcid | Hoenerhoff, MJ | |
dc.identifier.name-orcid | Lewis, TC | |
dc.identifier.name-orcid | Hershenson, MB; 0000-0001-9436-5593 | |
dc.working.doi | 10.7302/22080 | en |
dc.owningcollname | Pediatrics and Communicable Diseases, Department of |
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