Towards a crucial role for DC-SIGN in tuberculosis and beyond

The C-type lectin DC-SIGN has recently received considerable attention in the context of tuberculosis and other infectious diseases. Clinical investigations, together with genetic association studies, strongly support the notion that variation in the level of expression of DC-SIGN – but not changes in the structure of the protein – might have a strong impact on the susceptibility to and pathogenesis of several infectious diseases, including tuberculosis. In addition, efforts to decipher the evolutionary history of the gene encoding DC-SIGN clearly demonstrated that this gene is under strong selective constraints that have prevented the accumulation of amino acid changes over time. Altogether, these findings suggest that DC-SIGN might play a crucial part in host immunity to pathogens and possibly beyond, at an early stage of human development.