The binding of mycolic acids to galectin-3: a novel interaction between a host soluble lectin and trafficking mycobacterial lipids?
Understanding the molecular mechanism of host-pathogen interactions is the basis for drug design and vaccine development. The fine composition of mycolic acids (MA), the major constituents of Mycobacterium tuberculosis (Mtb) cell envelope, as well as other cell wall-associated lipids, contribute to determine the virulence of a given strain. However, endogenous receptors for mycolic acids on susceptible cells exposed to mycobacterial infections have not been fully identified. Here, we show that galectin-3, a multifunctional beta-galactoside binding lectin present mainly in the cytoplasm of inflammatory cells and also present on the cell surface, can recognize mycobacterial mycolic acids. MA can inhibit the lectin self-association but not its carbohydrate-binding abilities and can selectively interfere in the interaction of the lectin with its receptors on temperature-sensitive dendritic cell line, suggesting that galectin-3 could be involved in the recognition of trafficking mycolic acids and participate in their interaction with host cells.
Barboni
Erminia
E
Mycobacterial Division, National Institute for Medical Research, The Ridgway, London NW7 1AA, UK. ebarbon@nimr.mrc.ac.uk
Coade
Stephen
S
Fiori
Anna
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002240:Carbohydrate Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D006224:Cricetinae; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D037502:Galectin 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000032:analysis; D007700:Kinetics; D007797:Laminin / Q000378:metabolism; D037102:Lectins / Q000378:metabolism*; D008024:Ligands; D008055:Lipids / Q000502:physiology*; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D009161:Mycobacterium / Q000737:chemistry / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D009171:Mycolic Acids / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000032:analysis; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D020349:Surface Plasmon Resonance; D013696:Temperature; D019014:fas Receptor / Q000378:metabolism
D000911:Antibodies, Monoclonal; D037502:Galectin 3; D015850:Interleukin-6; D007797:Laminin; D037102:Lectins; D008024:Ligands; D008055:Lipids; D008070:Lipopolysaccharides; D009171:Mycolic Acids; D011506:Proteins; D011994:Recombinant Proteins; D019014:fas Receptor