Chapter 4: Molecular Basis of Mycobacterium tuberculosis Recognition by the C-Type Lectin DC-SIGN: from the Modulation of Innate Immune Response to the Design of Innovative Anti-inflammatory Drugs

The dendritic cell-specific intracellular adhesion molecule (ICAM)-3 grabbing non-integrin (DC-SIGN) is a C-type lectin receptor restricted to potent antigen-presenting cells and involved in multiple immune functions. Most particularly, it plays a role as a pattern recognition receptor for several viruses (HIV, Ebola, hepatitis C, cytomegalovirus and Dengue), parasites (Leishmania and Schistosoma mansoni) and bacteria (Mycobacterium tuberculosis, Helicobacter pylori and Klebsiella pneumoniae). We describe here DC-SIGN cell-type distribution and expression, structure and mechanisms of carbohydrate recognition, and functions, as well as associated signalling pathways. In addition, we discuss our current understanding of the molecular bases underlying the recognition by DC-SIGN of the major human pathogen M. tuberculosis. Finally, we illustrate how, by mimicking a strategy used by M. tuberculosis to undermine the host inflammatory response via targeting DC-SIGN, we were able to design innovative synthetic anti-inflammatory molecules.