title: Mycobacterium avium glycopeptidolipids require specific acetylation and methylation patterns for signaling through toll-like receptor 2.
abstract: Toll-like receptors (TLRs) recognize pathogen-associated molecules and play a vital role in promoting an immune response against invading microbes. TLR2, one of the key members of the TLR family, recognizes a wide variety of microbial products, including lipoproteins and lipopeptides, from a number of pathogens. Recent studies from our laboratory indicate that glycopeptidolipids (GPLs), a major surface component of Mycobacterium avium and other non-tuberculosis mycobacteria, are ligands for TLR2. However, the molecular requirements necessary for the GPL-TLR2 interaction were not defined in this report. In the present study we isolated different GPL species from M. avium, and using mass spectrometry and NMR analyses, characterized the molecular requirements of the GPL-TLR2 interaction. Interestingly, the extent of the respective acetylation and methylation of the 6-deoxytalose and rhamnose contained within the core GPL structure dictated whether the GPL signaled through TLR2. These experiments illustrate how subtle changes in a complex TLR2 ligand can alter its affinity for this important receptor, and suggest that M. avium could potentially modify its GPL structure to limit its interaction with TLR2.
authors.affiliation: Department of Biological Sciences, Eck Center for Global Health and Infectious Disease, University of Notre Dame, Indiana 46556, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Sweet
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhang
authors.forename: Heidi
authors.initials: H
authors.lastname: Torres-Fewell
authors.forename: Anthony
authors.initials: A
authors.lastname: Serianni
authors.forename: William
authors.initials: W
authors.lastname: Boggess
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schorey
mesh_terms: D000107:Acetylation; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D002240:Carbohydrate Sequence; D003837:Deoxy Sugars / Q000737:chemistry / Q000276:immunology; D006017:Glycolipids / Q000737:chemistry / Q000276:immunology*; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology*; D006601:Hexoses / Q000737:chemistry / Q000276:immunology; D008024:Ligands; D008264:Macrophages / Q000276:immunology*; D008745:Methylation; D051379:Mice; D009162:Mycobacterium avium / Q000737:chemistry / Q000276:immunology*; D012210:Rhamnose / Q000737:chemistry / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013329:Structure-Activity Relationship; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D003837:Deoxy Sugars; D006017:Glycolipids; D006023:Glycoproteins; D006601:Hexoses; D008024:Ligands; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C011754:6-deoxytalose; D012210:Rhamnose