Mediators involved in the regulation of responses to mycobacterial infections and inflammation
During inflammatory responses activation of mediators including inflammatory cytokines are critical. Several of these mediators are also required for protection against infections. Tumor Necrosis Factor (TNF), a cytokine activated by inflammatory responses, is also a key molecule required for host defense mechanisms against mycobacterial infections and elimination of invading bacteria. Our laboratory is interested in characterizing mediators involved in both host defense mechanisms and acute inflammatory responses. Using experimental animal models of infection and inflammation, we have shown that the membrane TNF variant protects from mycobacterial infections and play a limited role during inflammation. Based on these data, we have tested the hypothesis of selective inhibition of soluble TNF sparing membrane TNF and showed that this specific inhibition is effective against acute inflammatory responses while host defenses mechanisms against Mycobacterium tuberculosis and Mycobacterium bovis BCG involving granuloma formation is not altered. This strategy allows design new anti-inflammatory therapies with lower risk of infection compared to total inhibition of cytokines.
We are comparing the activity of other mediators to that of TNF in order to identify other molecules. We are investigating cellular sources of mediators, cells responding to factors and intracellular signaling. We are interested on the cellular mechanisms and factors involved in the process of activation and resolution of inflammatory and infectious diseases.