RSV infection-elicited high MMP-12–producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration

iScience

卷:24

Kisaburo Nagata¹  Yoshimasa Takahashi²  Chihiro Nakano²  Mashiro Nagayasu²  Toshiyo Nishimura³  Takehiko Shibata³  Toshihiro Ito⁴  Ikuo Hosoya⁵  Airi Makino⁵  Shigeki Nakamura⁶ 

[1] Corresponding author;

[2] Department of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan;

[3] Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan;

[4] Department of Microbiology, Tokyo Medical University, Tokyo 160-8402, Japan;

[5] Graduate School of Health Care Science, Bunkyo Gakuin University, Tokyo 113-8668, Japan;

关键词: Pathophysiology;    Immunology;    Virology;    Cell biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Respiratory 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.

【 授权许可】

Unknown