Dissecting the Role of Dectin-1 in the Interaction Between Mycobacteria and Macrophage

Previous studies indicate that infection of macrophages with pathogenic mycobacteria like M. tuberculosis and M. avium result in limited production of pro-inflammatory mediators relative to cells infected with attenuated or non-pathogenic mycobacteria. However, how the pathogenic and non-pathogenic mycobacteria elicit such different macrophage responses is unclear. Recent studies suggest a role for Dectin-1 in this differential response. Dectin-1 is a pattern recognition receptor that is expressed on macrophages and DCs, among others. Dectin-1 recognizes Ìøå¢-glucans found on various fungal species and is required for the macrophage production of the pro-inflammatory mediators following fungal infection. Recent studies in our laboratory indicate that Dectin-1 is also engaged upon macrophage infection with non-pathogenic mycobacteria and is required for the optimal macrophage pro-inflammatory response. Interestingly, pathogenic strains of M. avium and M. tuberculosis appear not to engage and/or signal through Dectin-1. To better address interaction between Dectin-1 and mycobacteria I initiated studies to: 1) define the ligand on M. smegmatis which engages Dectin-1 and 2) perform an initial characterization of the dectin-1 mediated signaling pathways activated upon mycobacterial infection