Related Experiment Video
Updated: Jul 12, 2026
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
USP18-driven macrophage M2 polarization through fatty acid β-oxidation inhibits immune responses induced by RSV
Dannv Yang1, Liyan Zhao1, Li Liu1
1Department of Pediatrics, Zhuji People's Hospital of Zhejiang Province, Zhuji City, China, 311800.
Introduction:
Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory infections in infants under six months, with limited treatment options available. Macrophages play a pivotal role in antiviral immunity, where their polarization state directly modulates immune responses.
Methodology:
The expression changes of ubiquitin-specific protease 18 (USP18) in RSV-infected samples were analyzed through the Gene Expression Omnibus database. An RSV infection model was established in C57BL/6 mice, and USP18 expression in lung tissues was measured by quantitative polymerase chain reaction (qPCR). Adenovirus-mediated USP18 knockdown was performed via tail vein injection, and its effects on immune cells were assessed using enzyme-linked immunosorbent assay (ELISA) and qPCR. THP-1 macrophage models with USP18 overexpression and knockdown were constructed. The effects of USP18 on macrophage polarization, immune function, and fatty acid β-oxidation during RSV infection were evaluated using immunofluorescence, ELISA, fatty acid oxidation (FAO) assays, boron-dipyrromethene (BODIPY) staining, and Western blot.
Results:
USP18 was markedly overexpressed in RSV-infected samples. USP18 knockdown in mice alleviated lung damage, reduced M2 macrophage markers, and enhanced CD8+ T cell activity. Cellular experiments demonstrated that USP18 promotes M2 macrophage polarization by enhancing fatty acid β-oxidation and regulating the expression of related enzymes, including ACLY, FASN, and ACC1. Elevated USP18 in macrophages during RSV infection inhibits CD8+ T cell activation, contributing to immune suppression. These effects were reversible with FAO inhibitors.
Conclusions:
USP18 upregulation in RSV-infected cells induces M2 macrophage polarization via fatty acid β-oxidation, thereby promoting immune suppression.
Insights
Ubiquitin-specific protease 18 (USP18) promotes M2 macrophage polarization and immune suppression during respiratory syncytial virus (RSV) infection by enhancing fatty acid oxidation. USP18 knockdown alleviates lung damage and enhances T cell activity in mice.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Respiratory syncytial virus (RSV) causes severe infant respiratory infections with limited treatments.
- Macrophages are key in antiviral immunity, with polarization state influencing immune response.
Purpose of the Study:
- To investigate the role of ubiquitin-specific protease 18 (USP18) in RSV infection.
- To determine USP18's effect on macrophage polarization and immune function during RSV infection.
Main Methods:
- Analyzed USP18 expression in RSV-infected samples via Gene Expression Omnibus database and mouse models (qPCR).
- Performed USP18 knockdown in mice and THP-1 macrophages (adenovirus-mediated, tail vein injection).
- Assessed macrophage polarization, immune function, and fatty acid oxidation (FAO) using ELISA, immunofluorescence, BODIPY staining, and Western blot.
Main Results:
- USP18 was overexpressed in RSV-infected samples.
- USP18 knockdown in mice reduced lung damage, M2 macrophage markers, and enhanced CD8+ T cell activity.
- USP18 promoted M2 macrophage polarization via enhanced fatty acid β-oxidation, inhibiting CD8+ T cell activation and causing immune suppression.
Conclusions:
- USP18 upregulation in RSV infection drives M2 macrophage polarization through fatty acid β-oxidation.
- This process contributes to immune suppression during RSV infection, highlighting USP18 as a potential therapeutic target.
Related Concept Videos
01:29Respiratory Syncytial Virus Disease
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...