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Macrophages and age-dependent resistance to hepatitis induced by herpes simplex virus type 2 im mice
Abstract:
An age-dependent increase in the resistance of BALB/c mice to induction of focal necrotic hepatitis by herpes simplex virus type 2 was demonstrated. In 3-week-old mice inoculated intraperitoneally with virus, numerous necrotic foci developed in the liver. As the mice matured, the number of lesions declined until the age of 8 weeks, when no further increase in resistance appeared. Corresponding to this, the virus titers of livers and spleens of 3-week-old mice were higher than in 8-week-old animals throughout the infection, and the infection was apparently terminated in these organs of the adult mice by day 5. In vitro infection of peritoneal macrophages from 3-week-old and 8-week-old mice showed that this age-related resistance was concomitant with an increased restriction of virus replication in peritoneal macrophages from adult mice. Since, furthermore, the resistance of adult mice could be abolished by intravenous inoculation of the macrophage-toxic agent silica before infection, and since adoptive transfer of 2 X 10(6) syngeneic macrophages from adult mice to young ones conferred to the latter a resistance comparable to that of the adult mice, it is concluded that macrophage maturation is responsible for the age-dependent resistance seen in this infection.
Insights
Young mice are more susceptible to herpes simplex virus type 2 (HSV-2) infection, developing liver damage. Macrophage maturation in older mice enhances resistance to HSV-2, limiting virus replication and disease severity.
Area of Science:
- Immunology
- Virology
- Pathology
Background:
- Herpes simplex virus type 2 (HSV-2) can cause severe disease, particularly in young individuals.
- Age-related differences in immune responses significantly impact viral infection outcomes.
Purpose of the Study:
- To investigate the age-dependent resistance of BALB/c mice to HSV-2-induced hepatitis.
- To elucidate the role of macrophages in this age-related resistance.
Main Methods:
- Induction of focal necrotic hepatitis in mice of varying ages (3-week-old vs. 8-week-old) using HSV-2.
- Quantification of viral titers in liver and spleen tissues.
- In vitro infection of peritoneal macrophages.
- Assessment of resistance following silica treatment or adoptive macrophage transfer.
Main Results:
- Younger (3-week-old) mice exhibited significantly more liver lesions and higher viral titers compared to older (8-week-old) mice.
- Peritoneal macrophages from adult mice showed restricted HSV-2 replication compared to those from young mice.
- Macrophage function was critical, as silica treatment abolished resistance in adult mice, while macrophage transfer conferred resistance to young mice.
Conclusions:
- Macrophage maturation is the key factor responsible for age-dependent resistance to HSV-2 infection in BALB/c mice.
- Mature macrophages exhibit an enhanced ability to restrict HSV-2 replication, thereby controlling the infection.