CONICET | Buscador de Institutos y Recursos Humanos

-Introduction Viral infections are a health problem worldwide. Virus triggered innate and adaptative immune responses in the host to control infection, but this defense mechanism can also damage host cells. Thus, antiviral immunity is a double-edge sword between immunoprotection and immunopathology, that is constantly regulated to avoid unnecessary damage. The inflammasomes play a crucial role in the innate immune response to viral infection through the recognition of viral RNA. They are multiproteins complexes that induce downstream immune responses after the encounter with pathogens, environmental stimuli, and/or cell damage. Once activated, they induced the activation of caspases and the release of mature proinflammatory interleukin-1b (IL-1beta). This production of proinflammatory cytokines is a critical step for an effective innate response, and is also a pivotal mechanism by which the innate immune system influences the development of adaptive immune responses. It has been established on different models that IL-lbeta activates lymphocytes and recruits leukocytes to the site of infection, and that this interaction is crucial to establish a proper T CD8+ cells antiviral immune response, and subsequent viral clearance. Then, a deeper understanding of this interaction will be an important step-forward in the development of treatment strategies to a variety of viral infection. Therefore, we have focused on the analysis of the association between antiviral immune response and inflammasome activation in a mouse model of viral hepatitis using Mouse Hepatitis Virus strain A 59 (MHV-A59). MHV-A59 is a single-stranded, positive-sense RNA virus belonging to the coronavirus family, that induces mild hepatitis in healthy adult mice. We also have been working on the characterization of Tmem176b, a cationic channel involved in CD8+ T cells promotion and inflammasome modulation. Thus, given de importance of these two branches on antiviral immunity and the relevance of their regulation to establish a balanced immune response, we also investigate the role of this novel immune regulator in this model of viral infection. Objective: To identify novel regulatory mechanisms to modulate antiviral immunity. In vitro: To determine if MHV-A59 infection induces inflammasome activation on BMDCs and characterize the role of Tmem176b in viral infection.In vivo: To analyze the importance of inflammasome in viral hepatitis and to define the relation between inflammasome/Tmem176b/antiviral immunity in vivo.

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