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Role of macrophage cytokines in influenza A virus infections
Abstract:
Human monocytes and murine macrophages were found to be susceptible to infection by influenza A virus. Although virus replication was low, infection led to cell death which was characterized by an extreme intracellular vacuolization. Most importantly, influenza A virus infection was accompanied by a particular pattern of cytokine release. Whereas IL-1 beta, IL-6 and TNF-alpha production was dependent on exposure to infectious virus, IFN-alpha/beta release was also induced by UV-inactivated virus. Although influenza A virus infection alone induced a substantial cytokine mRNA accumulation, translation into bioactive cytokine protein was rather limited. However, addition of low LPS concentrations was capable of strongly potentiating cytokine release from virus-infected cells. Thus, in a first step, an influenza A virus infection primes mononuclear phagocytes by leading to an accumulation of cytokine mRNA which, in a second step, may be readily translated into bioactive cytokines when triggering signals such as LPS are available. These findings suggest that influenza A virus represents an ultimately fatal macrophage activating factor which, when inducing moderate amounts of cytokines, may be beneficial by mounting an immediate antiviral response, but which may cause adverse effects when cytokine release is highly elevated by bacterial products.
Insights
Influenza A virus infects monocytes and macrophages, causing cell death and a specific cytokine release pattern. Bacterial products like LPS can amplify this response, potentially leading to adverse effects.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human monocytes and murine macrophages are susceptible to Influenza A virus infection.
- Infection leads to cell death with significant intracellular vacuolization.
- Influenza A virus infection triggers a distinct cytokine release profile.
Purpose of the Study:
- To investigate the effects of Influenza A virus infection on mononuclear phagocytes.
- To characterize the cytokine response following viral infection.
- To explore the potentiation of cytokine release by bacterial products.
Main Methods:
- Infection of human monocytes and murine macrophages with Influenza A virus.
- Analysis of cytokine production (IL-1 beta, IL-6, TNF-alpha, IFN-alpha/beta).
- Assessment of cytokine mRNA accumulation and protein translation.
- Evaluation of lipopolysaccharide (LPS) potentiation of cytokine release.
Main Results:
- Influenza A virus infection caused low replication but significant cell death and vacuolization.
- Infectious virus induced IL-1 beta, IL-6, and TNF-alpha; UV-inactivated virus induced IFN-alpha/beta.
- Viral infection led to cytokine mRNA accumulation but limited protein translation.
- Low concentrations of LPS strongly potentiated cytokine release from infected cells.
Conclusions:
- Influenza A virus primes mononuclear phagocytes by accumulating cytokine mRNA.
- Subsequent exposure to triggers like LPS facilitates cytokine protein translation.
- The virus acts as a macrophage activating factor, with potential benefits in antiviral response and risks of adverse effects when amplified by bacterial products.