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Marginal zone macrophages and immune responses against viruses
Stephan Oehen1, Bernhard Odermatt, Urs Karrer
1Institute for Experimental Immunology, University Hospital, Zurich, Switzerland. oehen@cytos.com
Abstract:
The effective establishment of antiviral protection requires a coordinated interplay between the innate and adaptive immune system. Using osteopetrotic (op(-/-)) mice, this study investigated the influence of marginal zone macrophages in controlling and initiating a protective immune response against a cytopathic vs a non- or low-cytopathic virus. Despite the generation of potent adaptive immune responses, antiviral protection against cytopathic vesicular stomatitis virus critically depended on the presence of marginal zone macrophages. Infection with low doses (100 PFU) of non- or low-cytopathic lymphocytic choriomeningitis virus was rarely cleared and usually resulted in a carrier state in the majority of mice. This shows that the early innate immune system provides an important preparatory phase to the adaptive immune system and is particularly important for antiviral protection.
Insights
Marginal zone macrophages are crucial for controlling viral infections, especially those caused by cytopathic viruses. The innate immune system
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Antiviral protection relies on coordinated innate and adaptive immune responses.
- Marginal zone macrophages (MZMs) play a role in immune surveillance and response initiation.
- Understanding MZM function is key to developing effective antiviral strategies.
Purpose of the Study:
- To investigate the role of MZMs in antiviral immunity against different types of viruses.
- To compare the impact of MZMs on responses to cytopathic versus non- or low-cytopathic viruses.
Main Methods:
- Utilized osteopetrotic (op(-/-)) mice, which lack MZMs.
- Infected mice with vesicular stomatitis virus (cytopathic) and lymphocytic choriomeningitis virus (low-cytopathic).
- Assessed the development of adaptive immune responses and viral clearance.
Main Results:
- Antiviral protection against cytopathic vesicular stomatitis virus was critically dependent on MZMs.
- Infection with low-dose lymphocytic choriomeningitis virus often resulted in a carrier state in mice lacking MZMs.
- Potent adaptive immune responses were generated but insufficient without MZMs for complete viral control.
Conclusions:
- MZMs are essential for effective antiviral protection, particularly against cytopathic viruses.
- The innate immune system, including MZMs, provides a critical preparatory phase for adaptive immunity.
- Early innate immune responses are vital for complete viral clearance and preventing chronic infection.