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Updated: Oct 15, 2025
An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
RSV infection-elicited high MMP-12-producing macrophages exacerbate allergic airway inflammation with neutrophil
Airi Makino1,2,3, Takehiko Shibata1,2,3, Mashiro Nagayasu2,3
1Department of Microbiology, Tokyo Medical University, Tokyo 160-8402, Japan.
Abstract:
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.
Insights
Respiratory syncytial virus (RSV) infection worsens asthma by increasing matrix metalloproteinase-12 (MMP-12). Inhibiting MMP-12 may offer a new asthma treatment strategy.
Area of Science:
- Immunology
- Respiratory Medicine
- Virology
Background:
- Respiratory syncytial virus (RSV) infection exacerbates bronchial asthma.
- No licensed RSV vaccine or specific treatments are currently available.
- Alveolar macrophages play a role in airway inflammation.
Purpose of the Study:
- To investigate the role of matrix metalloproteinase-12 (MMP-12) in RSV-induced asthma exacerbation.
- To explore MMP-12 as a potential therapeutic target for asthma.
Main Methods:
- Mice were subjected to allergic airway inflammation (house dust mite antigen - HDM) and infected with RSV.
- MMP-12 expression, viral load, neutrophil infiltration, and airway hyperresponsiveness (AHR) were measured.
- Mice were genetically deficient in MMP-12 or treated with an MMP-12 inhibitor (MMP408) or dexamethasone.
Main Results:
- RSV infection in HDM-sensitized mice significantly increased MMP-12, viral load, neutrophil infiltration, and AHR.
- These exacerbations were attenuated in MMP-12-deficient mice and those treated with MMP408.
- Dexamethasone treatment did not attenuate the exacerbations.
- M2-like macrophages were identified as producers of MMP-12, with production promoted by RSV-induced IFN-β and IL-4 receptor expression.
Conclusions:
- RSV-induced MMP-12 production by alveolar macrophages exacerbates allergic airway inflammation and asthma.
- Targeting MMP-12 presents a novel therapeutic strategy for managing RSV-associated asthma exacerbations.
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