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Updated: Dec 3, 2025
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
MAVS Deficiency Is Associated With a Reduced T Cell Response Upon Secondary RSV Infection in Mice
Michelle Paulsen1, Augusto Varese1, Nawamin Pinpathomrat1
1Respiratory Infections Section, St Mary's Campus, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Abstract:
Infections with respiratory syncytial virus (RSV) occurs repeatedly throughout life because sustained, protective memory responses fail to develop. Why this occurs is not known. During RSV infection the recognition of the virus via the cytosolic RIG-I like receptors and signaling via the adaptor protein MAVS is crucial for mounting an innate immune response. However, if this signaling pathway is important for T cell responses during primary infection and during re-infection is not fully elucidated. We describe a second peak of pro-inflammatory mediators during the primary immune response to RSV that coincides with the arrival of T cells into the lung. This second peak of cytokines/chemokines is regulated differently than the early peak and is largely independent of signaling via MAVS. This was concurrent with Mavs-/- mice mounting a strong T cell response to primary RSV infection, with robust IFN-γ; and Granzyme B production. However, after RSV re-infection, Mavs-/- mice showed fewer CD4+ and CD8+ short term memory T cells and their capacity to produce IFN-γ; and Granzyme B, was decreased. In sum, cytosolic recognition of RSV is important not only for initiating innate anti-viral responses but also for generating or maintaining efficient, short term T cell memory responses.
Insights
Respiratory syncytial virus (RSV) reinfection occurs because MAVS-independent pathways are crucial for T cell memory. Cytosolic viral recognition impacts both innate immunity and short-term T cell memory generation.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Respiratory syncytial virus (RSV) causes recurrent infections due to a lack of lasting protective memory responses.
- The cytosolic RIG-I-like receptor (RLR) and MAVS signaling pathway is vital for innate immunity during RSV infection.
- The role of MAVS signaling in T cell responses during primary and secondary RSV infections remains unclear.
Purpose of the Study:
- To investigate the role of MAVS-dependent signaling in T cell responses during primary and re-infection with RSV.
- To understand the mechanisms underlying the failure of sustained protective memory responses to RSV.
Main Methods:
- Utilized a mouse model lacking MAVS (Mavs-/-) to assess T cell responses following primary and secondary RSV infections.
- Analyzed the production of pro-inflammatory mediators, cytokines (IFN-γ), and cytotoxic molecules (Granzyme B).
- Quantified CD4+ and CD8+ T cell populations to evaluate short-term memory formation.
Main Results:
- Mavs-/- mice mounted a strong T cell response during primary RSV infection, with robust IFN-γ and Granzyme B production.
- A second peak of pro-inflammatory mediators during primary infection was observed, largely independent of MAVS signaling.
- Following RSV re-infection, Mavs-/- mice exhibited reduced numbers of short-term memory CD4+ and CD8+ T cells and diminished IFN-γ and Granzyme B production.
Conclusions:
- Cytosolic recognition of RSV is essential for initiating innate antiviral responses.
- MAVS-independent pathways play a significant role in T cell responses during primary RSV infection.
- Effective generation and maintenance of short-term T cell memory to RSV are dependent on MAVS signaling.
