Prof. Irène Garcia-Gabay
Tuberculosis infection is still a major health issue. Recently the reactivation of controlled or latent TB infection due to immunosuppression and the use of several novel therapies for autoimmune diseases including rheumatoid arthritis has attracted substantial interest and concerns. We have shown previously that TNF neutralization may reactivate latent TB infection. With recent interest in IL-1 neutralization therapies we need to investigate in depth the role of the IL-1 pathway in bacterial infections.
We propose to study this pathway in host response to virulent Mycobacterium tuberculosis as well as the attenuated vaccine strain Mycobacterium bovis BCG, and Listeria monocytogenes, all intracellular pathogens with different virulence for the host.. The following aspects are investigated:
- In vitro production of IL-1b and inflammasome activation in macrophages from wild-type BL6, NLPR3, ASC or capspase-1 deficient mice
- Control of infection in BL6, IL-1a/b, IL-1R1, NLPR3, ASC or capspase-1 deficient mice
- Induction of an adaptive and memory response in the absence of IL-1 or NLPR3 inflammasome complex
- Investigation on the molecular mechanism of the activation of the NLPR3 inflammasome