文章基本信息

标题：RSV infection-elicited high MMP-12–producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration
本地全文：下载
作者：Airi Makino ; Takehiko Shibata ; Mashiro Nagayasu 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：10
页码：1-21
DOI：10.1016/j.isci.2021.103201
语种：English
出版社：Elsevier
摘要：SummaryRespiratory syncytial virus (RSV) infection often exacerbates bronchial asthma, but there is no licensed RSV vaccine or specific treatments. Here we show that RSV-induced alveolar macrophages, which produce high levels of matrix metalloproteinase-12 (MMP-12), exacerbate allergic airway inflammation with increased neutrophil infiltration. When mice subjected to allergic airway inflammation via exposure to the house dust mite antigen (HDM) were infected with RSV (HDM/RSV), MMP-12 expression, viral load, neutrophil infiltration, and airway hyperresponsiveness (AHR) were increased compared to those in the HDM and RSV groups. These exacerbations in the HDM/RSV group were attenuated in MMP-12-deficient mice and mice treated with MMP408, a selective MMP-12 inhibitor, but not in mice treated with dexamethasone. Finally, M2-like macrophages produced MMP-12, and its production was promoted by increase of IFN-β-induced IL-4 receptor expression with RSV infection. Thus, targeting MMP-12 represents a potentially novel therapeutic strategy for the exacerbation of asthma.Graphical abstractDisplay OmittedHighlights•RSV–induced MMP-12 exacerbates allergic airway inflammation•RSV–elicited IL-4RαhighM2-like macrophages highly express MMP-12•MMP-12 enhances neutrophil infiltration via promotion of IL-17A and CXCL1 production•MMP-12 inhibitor attenuates RSV-induced neutrophilic airway inflammationPathophysiology; Immunology; Virology; Cell biology