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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
Adenovirus induces pediatric pneumonia via triggering macrophage polarization and IL-6 production via NF-κB
Xiaoping Yuan1, Haoying Huang2, Huifeng Fan3
1Department of Respiratory Medicine, School of Pharmaceutical Sciences, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Research Center for Child Health, Guangzhou 510623, China; Guangzhou Women and Children's Medical Center, Guangdong Provincial Research Center for Child Health, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510623, China.
Abstract:
Human adenovirus (HAdV) is one of major pathogens that causes acute respiratory infections in children. Pulmonary macrophages mediated pulmonary immune response is crucial in both host defense against HAdV and lung pathogenesis. However, the specific role of macrophage polarization in HAdV-induced lung injury remains unclear. Here, using bulk RNA-sequencing of bronchoalveolar lavage fluid (BALF) cells from children with HAdV pneumonia, we found that adenovirus infection upregulates the genes associated with macrophage polarization. Flow cytometry revealed a significantly higher proportion of M1 macrophages in severe cases compared to the non-severe cases. Mechanistically, in vitro infection of a human macrophage cell line demonstrated that HAdV directly induces M1 polarization and stimulates the production of inflammatory cytokine IL-6 via NF-κB activation. Our findings demonstrate that HAdV infection drives M1 macrophage polarization and IL-6 production through NF-κB signaling pathway, elucidating a key mechanism underlying the excessive inflammation and lung injury in severe HAdV infection.
Insights
Human adenovirus (HAdV) infection in children drives M1 macrophage polarization, increasing IL-6 production via NF-κB signaling. This mechanism contributes to severe lung injury in HAdV pneumonia.
Area of Science:
- Immunology
- Virology
- Pediatric Respiratory Diseases
Background:
- Pulmonary macrophages are key in antiviral defense and lung pathogenesis.
- Macrophage polarization's role in adenovirus-induced lung injury is not fully understood.
Purpose of the Study:
- To investigate the role of macrophage polarization in children with HAdV pneumonia.
- To elucidate the molecular mechanisms of HAdV-induced lung injury.
Main Methods:
- Bulk RNA-sequencing of bronchoalveolar lavage fluid (BALF) cells.
- Flow cytometry analysis of macrophage populations.
- In vitro infection of human macrophage cell lines.
Main Results:
- Adenovirus infection upregulates genes linked to macrophage polarization.
- Severe HAdV pneumonia cases show a higher proportion of M1 macrophages.
- HAdV directly induces M1 polarization and IL-6 production via NF-κB activation in vitro.
Conclusions:
- HAdV infection promotes M1 macrophage polarization and IL-6 release.
- NF-κB signaling is a critical pathway in HAdV-driven inflammation and lung injury.
- Understanding this mechanism offers insights into severe HAdV infection pathogenesis.
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