Early-life heterologous rhinovirus infections induce an exaggerated asthma-like phenotype

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:146

Article

Rajput, Charu¹  Han, Mingyuan¹  Ishikawa, Tomoko¹  Lei, Jing¹  Jazaeri, Seyedehzarifeh¹  Bentley, J. Kelley¹  Hershenson, Marc B.^1,2 

[1] Univ Michigan, Sch Med, Dept Pediat, Ann Arbor, MI USA

[2] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI USA

关键词: Asthma;    childhood;    early-life;    IL-13;    rhinovirus;    RV-A1B;    RV-A2;    trained immunity;    type 2 innate lymphoid cell;    ILC2;   

DOI  :  10.1016/j.jaci.2020.03.039

来源: Elsevier

【 摘 要 】

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 Rora(fl/fl)Il7r(cre) 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-gamma 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-gamma 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, GobS, Muc5b, and Muc5ac mRNA; increased numbers of eosinophils and IL-13-producing ILC2s; and exaggerated mucus metaplasia and airway hyperresponsiveness. Compared with Rora(fl/fl) mice, Rora(fl/fl)Il7r(cre) 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.

【 授权许可】

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