DC-SIGN and mannosylated surface structures of Mycobacterium tuberculosis: a deceptive liaison.
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is recognized by pattern recognition receptors on macrophages and dendritic cells, thereby triggering phagocytosis, antigen presentation to T cells and cytokine secretion. The dendritic cell-specific intercellular adhesion molecule 3 grabbing nonintegrin (DC-SIGN) is a calcium-dependent carbohydrate-binding protein with specificity for mannose-containing glycoconjugates and fucose-containing Lewis antigens. Mannosylated moieties of the mycobacterial cell wall, such as mannose-capped lipoarabinomannan (manLAM) or higher-order phosphatidylinositol-mannosides (PIMs) of Mtb, were previously shown to bind to DC-SIGN on immature dendritic cells and macrophage subpopulations. This interaction reportedly impaired dendritic cell maturation, modulated cytokine secretion by phagocytes and dendritic cells and was postulated to cause suppression of protective immunity to TB. However, experimental Mtb infections in mice transgenic for human DC-SIGN revealed that, instead of favoring immune evasion of mycobacteria, DC-SIGN may promote host protection by limiting tissue pathology. Furthermore, infection studies with mycobacterial strains genetically engineered to lack manLAM or PIMs demonstrated that the manLAM/PIM-DC-SIGN interaction was not critical for cytokine secretion in vitro and protective immunity in vivo. The dominant Mtb-derived ligands for DC-SIGN are presently unknown, and a major role of DC-SIGN in the immune response to Mtb infection may lie in its capacity to maintain a balanced inflammatory state during chronic TB.
Ehlers
Stefan
S
Microbial Inflammation Research, Research Center Borstel, Parkallee 1, 23845 Borstel, Germany. sehlers@fz-borstel.de
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000166:cytology* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013499:Surface Properties; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008358:Mannose; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin