Deficient inflammasome activation permits an exaggerated asthma phenotype in rhinovirus C-infected immature mice.
Mucosal Immunol
; 14(6): 1369-1380, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34354243
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-1ß. 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-1ß and NLRP3) were not different between the two viruses. However, inflammasome activation (mature IL-1ß 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-1ß 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-1ß are deficient, permitting exaggerated type 2 inflammation and mucous metaplasia.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
/
Asma
/
Enterovirus
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Infecções por Coxsackievirus
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Inflamassomos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mucosal Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos