Early-life heterologous rhinovirus infections induce an exaggerated asthma-like phenotype.
J Allergy Clin Immunol
; 146(3): 571-582.e3, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32344055
ABSTRACT
BACKGROUND:
Early-life wheezing-associated respiratory tract infection by rhinovirus (RV) is a risk factor for asthma development. Infants are infected with many different RV strains per year.OBJECTIVE:
We previously showed that RV infection of 6-day-old BALB/c mice induces a mucous metaplasia phenotype that is dependent on type 2 innate lymphoid cells (ILC2s). We hypothesized that early-life RV infection alters the response to subsequent heterologous infection, inducing an exaggerated asthma-like phenotype.METHODS:
Wild-type BALB/c mice and Rorafl/flIl7rcre mice lacking ILC2s were treated as follows (1) sham on day 6 of life plus sham on day 13 of life, (2) RV-A1B on day 6 plus sham on day 13, (3) sham on day 6 plus RV-A2 on day 13, and (4) RV-A1B on day 6 plus RV-A2 on day 13.RESULTS:
Mice infected with RV-A1B at day 6 and sham at day 13 showed an increased number of bronchoalveolar lavage eosinophils and increased expression of IL-13 mRNA but not expression of IFN-γ mRNA (which is indicative of a type 2 immune response), whereas mice infected with sham on day 6 and RV-A2 on day 13 of life demonstrated increased IFN-γ expression (which is a mature antiviral response). In contrast, mice infected with RV-A1B on day 6 before RV-A2 infection on day 13 showed increased expression of IL-13, IL-5, Gob5, Muc5b, and Muc5ac mRNA; increased numbers of eosinophils and IL-13-producing ILC2s; and exaggerated mucus metaplasia and airway hyperresponsiveness. Compared with Rorafl/fl mice, Rorafl/flIl7rcre mice showed complete suppression of bronchoalveolar lavage eosinophils and mucous metaplasia.CONCLUSION:
Early-life RV infection alters the response to subsequent heterologous infection, inducing an intensified asthma-like phenotype that is dependent on ILC2s.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Rhinovirus
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Infecções por Picornaviridae
/
Células Th2
/
Eosinófilos
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
/
Newborn
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2020
Tipo de documento:
Article