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Age-dependent resistance of human alveolar macrophages to herpes simplex virus
Abstract:
Studies in mice demonstrate an age-dependent susceptibility to disseminated herpesvirus infection which is mediated. at least in part, by a defect in macrophage antiviral function. We examined the growth of herpes simplex virus within human alveolar macrophages obtained by bronchopulmonary lavage from neonates, adults with a variety of immunosuppressive disorders, and healthy adult volunteers. At 24 h postinfection, mean viral titers in neonatal macrophages increased 19-fold over adsorbed virus levels, a highly significant increase when compared to either immunosuppressed or normal adult macrophages (P less than 0.0005). These findings indicate that human macrophages, like those of mice, exhibit age-dependent permissiveness for the replication of herpes simplex virus. This permissiveness may at least partially account for the clinical observation that human newborns are highly susceptible to disseminated herpes simplex virus infections, whereas adults are not.
Insights
Neonatal macrophages are highly permissive to herpes simplex virus replication, unlike adult macrophages. This age-dependent difference in viral susceptibility may explain why newborns are more vulnerable to disseminated herpes simplex virus infections.
Area of Science:
- Immunology
- Virology
- Neonatal Medicine
Background:
- Age-dependent susceptibility to disseminated herpesvirus infections is observed in mice, linked to macrophage antiviral defects.
- Herpes simplex virus (HSV) infections pose a significant risk to newborns, with higher rates of disseminated disease compared to adults.
Purpose of the Study:
- To investigate the age-dependent permissiveness of human alveolar macrophages to herpes simplex virus (HSV) replication.
- To compare HSV replication in macrophages from neonates, immunosuppressed adults, and healthy adults.
Main Methods:
- Human alveolar macrophages were obtained via bronchopulmonary lavage from neonates and adults (immunosuppressed and healthy).
- Macrophages were infected with herpes simplex virus, and viral titers were measured at 24 hours postinfection.
Main Results:
- Neonatal macrophages showed a 19-fold increase in viral titers compared to adsorbed virus levels.
- This increase in viral replication was significantly higher (P < 0.0005) in neonatal macrophages than in adult macrophages (both immunosuppressed and healthy).
Conclusions:
- Human alveolar macrophages exhibit age-dependent permissiveness to herpes simplex virus replication, mirroring findings in mice.
- This macrophage permissiveness in neonates may contribute to their increased susceptibility to disseminated herpes simplex virus infections.