Related Experiment Videos
Requirement for macrophages for interferon to be effective against encephalomyocarditis virus infection of mice
Abstract:
Suppression of macrophages in mice by treatments with silica or auro-thiomalate (Myocrisin) reduced production of serum interferon by polyriboinosinic acid:polyribocytidylic acid by 85 to 90%, indicating that this double-stranded polynucleotide caused interferon production primarily in macrophages. Suppression of macrophages in mice by silica or Myocrisin treatment did not significantly affect the susceptibility of mice to encephalomyocarditis virus, although at virus doses around 20 times the 50% lethal dose they died about 48 h earlier. Macrophage interferon protected mice from encephalomyocarditis virus infection at much lower doses than fibroblast interferon, and treatment of mice with silica or Myocrisin abolished the protection conferred by macrophage interferon, whereas these treatments had a much smaller effect on the protection afforded by fibroblast interferon. The requirement for macrophages for interferon to be effective in mice can explain why macrophage suppression can cause normally nonlethal viruses to kill adult mice.
Insights
Macrophages are key to producing interferon, a crucial antiviral defense. Suppressing these immune cells impairs the body's ability to fight certain viruses, potentially leading to severe illness.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Interferons are critical cytokines in antiviral immunity.
- Macrophages are known to produce interferons in response to viral stimuli.
- The specific role of macrophages in mediating interferon's protective effects against viral infections requires further elucidation.
Purpose of the Study:
- To investigate the role of macrophages in the production of serum interferon induced by polyriboinosinic acid:polyribocytidylic acid.
- To determine the impact of macrophage suppression on the susceptibility of mice to encephalomyocarditis virus.
- To compare the protective efficacy of macrophage-derived interferon versus fibroblast-derived interferon in vivo.
Main Methods:
- Mice were treated with silica or aurothiomalate (Myocrisin) to suppress macrophage activity.
- Serum interferon levels were measured after stimulation with polyriboinosinic acid:polyribocytidylic acid.
- Mice were infected with encephalomyocarditis virus to assess viral susceptibility and survival.
- The protective effects of macrophage and fibroblast interferons were evaluated in both normal and macrophage-suppressed mice.
Main Results:
- Macrophage suppression by silica or Myocrisin significantly reduced serum interferon production by 85-90% following polyriboinosinic acid:polyribocytidylic acid stimulation.
- Macrophage suppression did not significantly alter susceptibility to encephalomyocarditis virus, though mice succumbed slightly faster at high doses.
- Macrophage-derived interferon provided potent protection against encephalomyocarditis virus, which was abolished by macrophage suppression.
- Fibroblast interferon offered less protection, and its efficacy was only minimally affected by macrophage suppression.
Conclusions:
- Macrophages are the primary producers of serum interferon induced by polyriboinosinic acid:polyribocytidylic acid.
- Macrophage-derived interferon plays a critical role in protecting mice against encephalomyocarditis virus infection.
- The essential role of macrophages in mediating interferon's antiviral efficacy explains why their suppression can render normally non-lethal viruses fatal.