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Influenza A virus infects macrophages and stimulates release of tumor necrosis factor-alpha
Abstract:
The clinical picture of influenza A virus infections indicates that release of tumor necrosis factor-alpha (TNF-alpha) may be involved. In the present study we exposed the murine macrophage line PU5-1.8 to influenza A virus and observed a productive infection which was followed by subsequent cell death. Infection of macrophages was accompanied by TNF-alpha mRNA accumulation and TNF-alpha release. TNF-alpha production could only be induced by live virus whereas interferon release was also stimulated by inactivated virus. When virus-infected macrophages were exposed to low amounts of lipopolysaccharide (LPS; 1-10 ng/ml) TNF-alpha production was strongly potentiated. These data show that low LPS concentrations could readily trigger a high TNF-alpha release from influenza-A-virus-infected macrophages which could, at least partially, explain the serious complications of combined influenza A virus and bacterial infections.
Insights
Influenza A virus infection in macrophages triggers tumor necrosis factor-alpha (TNF-alpha) release. Low levels of lipopolysaccharide (LPS) significantly amplify this TNF-alpha response, potentially explaining severe outcomes in combined infections.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Influenza A virus infections are associated with clinical manifestations suggesting a role for tumor necrosis factor-alpha (TNF-alpha).
- Macrophages are key immune cells involved in the host response to viral pathogens.
Purpose of the Study:
- To investigate the production of TNF-alpha by macrophages infected with influenza A virus.
- To determine the effect of lipopolysaccharide (LPS) on TNF-alpha release from virus-infected macrophages.
Main Methods:
- Murine macrophage cell line (PU5-1.8) was infected with influenza A virus.
- Analysis of TNF-alpha mRNA accumulation and protein release.
- Assessment of interferon release.
- Exposure of infected macrophages to varying concentrations of LPS.
Main Results:
- Influenza A virus infection led to productive infection, cell death, TNF-alpha mRNA accumulation, and TNF-alpha release in macrophages.
- Only live influenza A virus induced TNF-alpha production, while inactivated virus stimulated interferon release.
- Low concentrations of LPS (1-10 ng/ml) strongly potentiated TNF-alpha production in virus-infected macrophages.
Conclusions:
- Influenza A virus infection induces TNF-alpha production in macrophages.
- Co-infection with bacteria, characterized by low LPS levels, can lead to significantly enhanced TNF-alpha release.
- This potentiation of TNF-alpha may contribute to the severe complications observed in combined influenza A virus and bacterial infections.