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Interaction of mouse peritoneal macrophages with fixed rabies virus in vivo and in vitro
Abstract:
The resistance of mice to intraperitoneal and intramuscular infection with fixed rabies virus increases with age. Treatment of mature animals with either silica, indian ink or antimacrophage serum, which are cytotoxic for macrophages, reduced their resistance to intraperitoneal, but not to intramuscular or intracerebral infection. Transfer of peritoneal macrophages from adults to syngeneic suckling mice delayed but did not prevent mortality from intraperitoneal infection: transfer of peritoneal macrophages to intramuscular sites of infection did not protect adult mice. Rabies virus was phagocytosed by peritoneal macrophages in culture but neither replicated nor induced interferon. Evidence of active intracellular destruction of virus was obscured by thermal inactivation at 37 degrees C. Less inactivation occurred at 33 degrees C. Infected macrophages from suckling mice, but not those from adult mice, spread infection to susceptible cells.
Insights
As mice age, their resistance to rabies virus infection increases. Macrophage function is crucial for intraperitoneal rabies immunity, with young macrophages spreading infection more effectively.
Area of Science:
- Immunology
- Virology
- Neuroscience
Background:
- The resistance of mice to fixed rabies virus infection increases with age.
- Macrophages play a role in the immune response to viral infections.
Purpose of the Study:
- To investigate the role of macrophages in age-dependent resistance to rabies virus infection.
- To determine the effect of macrophage-depleting agents and macrophage transfer on rabies virus infection outcomes.
Main Methods:
- Mice of different ages were infected with rabies virus.
- Macrophage function was modulated using silica, indian ink, and antimacrophage serum.
- Peritoneal macrophages from adult mice were transferred to suckling mice.
- Rabies virus interaction with macrophages was studied in vitro.
Main Results:
- Treatment with macrophage-cytotoxic agents reduced resistance to intraperitoneal infection in mature mice.
- Macrophage transfer from adults to sucklings delayed mortality from intraperitoneal infection.
- In vitro, macrophages phagocytosed rabies virus but did not support replication or interferon induction.
- Infected macrophages from suckling mice, unlike adult mice, spread infection to susceptible cells.
Conclusions:
- Macrophages are critical for age-dependent resistance to intraperitoneal rabies virus infection.
- Young macrophages are less effective at controlling rabies virus and may contribute to disease spread.
