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Published on: July 11, 2015
Interferon production by Corynebacterium parvum and BCG-activated murine spleen macrophages
Abstract:
Macrophages were identified to be a major source of interferon produced in murine spleen cell cultures after intravenous injection of Corynebacterium parvum (C. parvum), strain CN 6134 or Bacille Calmette Guérin (BCG). Another strain of C. parvum, CN 5888, which lacks RES stimulating activity and adjuvant activity in vivo, was not effective when injected intravenously. Protein synthesis was required for interferon activity to be produced and protein synthesis was also required for the antiviral state to be expressed. The antiviral activity was relatively stable to pH 2 and neutralized by an antiserum against virus-induced fibroblast interferon, thus exhibiting some properties of type I interferon. In vitro only CN 6134, the biologically active strain, could induce small amounts of interferon in spleen macrophage cultures. Macrophages from CN 6134 or BCG-infected athymic nu/nu mice produced similar interferon titers as their controls. It is concluded that infection with certain immunomodulators can activate splenic macrophages via a predominantly T-cell independent mechanism. Interferon in turn may operate locally as a mediator of immunoregulation.
Insights
Certain immunomodulators like Corynebacterium parvum activate splenic macrophages, a key source of interferon. This interferon production is largely T-cell independent and may regulate immune responses.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Macrophages are crucial immune cells involved in host defense.
- Interferons are critical signaling proteins in the innate immune system.
- Immunomodulators are agents that modify immune responses.
Purpose of the Study:
- To investigate the role of macrophages as a source of interferon following immunomodulator administration.
- To explore the mechanism of interferon induction and its properties.
- To determine the T-cell dependency of this immune response.
Main Methods:
- Murine spleen cell cultures were used to assess interferon production.
- Intravenous injection of Corynebacterium parvum (C. parvum) strains and Bacille Calmette Guérin (BCG) were employed.
- Protein synthesis inhibition and antiviral assays were performed.
- Characterization of interferon activity included pH stability and neutralization studies.
Main Results:
- Macrophages were identified as a major source of interferon after C. parvum (strain CN 6134) or BCG injection.
- A biologically inactive C. parvum strain (CN 5888) did not induce significant interferon.
- Protein synthesis was essential for both interferon production and the expression of the antiviral state.
- The induced interferon exhibited properties consistent with type I interferon.
- Interferon production was similar in athymic nu/nu mice, suggesting a T-cell independent mechanism.
Conclusions:
- Certain immunomodulators activate splenic macrophages to produce interferon through a T-cell independent pathway.
- Interferon may function as a local mediator in immunoregulation.
- The findings highlight the interplay between immunomodulators, macrophages, and interferon in innate immunity.
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