Neonatal Rhinovirus Infection Induces Mucous Metaplasia and Airways Hyperresponsiveness
| Autor: | Ying Zhao, J. Kelley Bentley, Emily R. Bowman, Nicholas W. Lukacs, Dina Schneider, Alan M. McLean, Jeffrey L. Curtis, Marc B. Hershenson, Joanne Sonstein, Marisa J. Linn, Jason B. Weinberg, Antonia P. Popova, Jun Young Hong, Uma S. Sajjan |
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| Rok vydání: | 2012 |
| Předmět: |
Respiratory Mucosa
Pathology medicine.medical_specialty Immunology Inflammation Cell Separation Biology Real-Time Polymerase Chain Reaction medicine.disease_cause Article Allergic sensitization Mice Immune system Metaplasia Respiratory Hypersensitivity medicine Animals Immunology and Allergy Mice Inbred BALB C Picornaviridae Infections respiratory system Flow Cytometry Immunohistochemistry Animals Newborn Cytokines Methacholine Rhinovirus medicine.symptom medicine.drug |
| Zdroj: | The Journal of Immunology. 188:2894-2904 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1101391 |
| Popis: | Recent studies link early rhinovirus (RV) infections to later asthma development. We hypothesized that neonatal RV infection leads to an IL-13–driven asthma-like phenotype in mice. BALB/c mice were inoculated with RV1B or sham on day 7 of life. Viral RNA persisted in the neonatal lung up to 7 d postinfection. Within this time frame, IFN-α, -β, and -γ peaked 1 d postinfection, whereas IFN-λ levels persisted. Next, we examined mice on day 35 of life, 28 d after initial infection. Compared with sham-treated controls, virus-inoculated mice demonstrated airways hyperresponsiveness. Lungs from RV-infected mice showed increases in several immune cell populations, as well as the percentages of CD4-positive T cells expressing IFN-γ and of NKp46/CD335+, TCR-β+ cells expressing IL-13. Periodic acid-Schiff and immunohistochemical staining revealed mucous cell metaplasia and muc5AC expression in RV1B- but not sham-inoculated lungs. Mucous metaplasia was accompanied by induction of gob-5, MUC5AC, MUC5B, and IL-13 mRNA. By comparison, adult mice infected with RV1B showed no change in IL-13 expression, mucus production, or airways responsiveness 28 d postinfection. Intraperitoneal administration of anti–IL-13 neutralizing Ab attenuated RV-induced mucous metaplasia and methacholine responses, and IL-4R null mice failed to show RV-induced mucous metaplasia. Finally, neonatal RV increased the inflammatory response to subsequent allergic sensitization and challenge. We conclude that neonatal RV1B infection leads to persistent airways inflammation, mucous metaplasia, and hyperresponsiveness, which are mediated, at least in part, by IL-13. |
| Databáze: | OpenAIRE |
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