Early-life wheezing-Associated infections with rhinovirus (RV) have been associated with asthma development in children. We have shown that RV infection of 6-day-old mice induces mucous metaplasia and airways hyperresponsiveness, which is dependent on IL-13, IL-25, and type 2 innate lymphoid cells (ILC2s). Infection of immature mice fails to induce lung IFN-g expression, in contrast to mature 8-week-old mice with a robust IFN-g response, consistent with the notion that deficient IFN-g production in immature mice permits RV-induced type 2 immune responses. We therefore examined the effects of intranasal IFN-g administration on RVinduced ILC2 expansion and IL-13 expression in 6-day-old BALB/c and IL-13 reporter mice. Airway responses were assessed by histology, immunofluorescence microscopy, quantitative polymerase chain reaction, ELISA, and flow cytometry. Lung ILC2s were also treated with IFN-g ex vivo.We found that, compared with untreated RV-infected immature mice, IFN-g treatment attenuated RV-induced IL-13 and Muc5acmRNAexpression and mucous metaplasia. IFN-g also reduced ILC2 expansion and the percentage of IL-13-secreting ILC2s. IFN-g had no effect on the mRNA or protein expression of IL-25, IL-33, or thymic stromal lymphoprotein. Finally, IFN-g treatment of sorted ILC2s reduced IL-5, IL-13, IL-17RB, ST2, and GATA-3 mRNA expression. We conclude that, in immature mice, IFN-g inhibits ILC2 expansion and IL-13 expression in vivo and ex vivo, thereby attenuating RV-induced mucous metaplasia. These findings demonstrate the antagonistic function of IFN-g on ILC2 expansion and gene expression, the absence of which may contribute to the development of an asthma-like phenotype after early-life RV infection.
|Number of pages||10|
|Journal||American Journal of Respiratory Cell and Molecular Biology|
|Publication status||Published - 2017 Feb|
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health HL081420 and AI120526 (M.B.H.).
© 2017 by the American Thoracic Society.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Pulmonary and Respiratory Medicine
- Clinical Biochemistry
- Cell Biology