Faculty Opinions recommendation of Neonatal rhinovirus induces mucous metaplasia and airways hyperresponsiveness through IL-25 and type 2 innate lymphoid cells.
Year: 2017
Type: peer-review
Abstract: Background-Early-life human rhinovirus (RV) infection has been linked to asthma development in high risk infants and children.Nevertheless, the role of RV infection in the initiation of asthma remains unclear.Objective-We hypothesized that, in contrast to infection of mature BALB/c mice, neonatal infection with RV promotes an IL-25-driven type 2 response which causes persistent mucous metaplasia and airway hyperresponsiveness.Methods-Six day-old and eight week-old BALB/c mice were inoculated with sham HeLa cell lysate or RV.Airway responses from 1 to 28 days after infection were assessed by qPCR, ELISA, histology, immunofluorescence microscopy, flow cytometry and methacholine responsiveness.Selected mice were treated with a neutralizing antibody to IL-25.Results-Compared to mature mice, RV infection in neonatal mice increased lung IL-13 and IL-25 production whereas IFN-γ, IL-12p40 and TNF-α expression were suppressed.In addition, the population of IL-13-secreting type 2 innate lymphoid cells (ILC2s) was expanded with RV infection in neonatal but not in mature mice.ILC2 cells were the major cell type secreting IL-13 in neonates.Finally, anti-IL-25 neutralizing antibody attenuated ILC2 expansion, mucous hypersecretion and airways responsiveness.Conclusions-These findings suggest that early-life viral infection could contribute to asthma development by provoking age-dependent, IL-25-driven type 2 immune responses.
Author: Johan Neyts
Institution: Rega Institute for Medical Research
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4255678505