Overexpression of proinflammatory TLR-2-signalling lipoproteins in hypervirulent mycobacterial variants.
Copyright policy )Overexpression of proinflammatory TLR-2-signalling lipoproteins in hypervirulent mycobacterial variants.
Changes in the cell envelope composition of mycobacteria cause major changes in cytokine profiles of infected antigen presenting cells. We describe here the modulation of inflammatory responses by Mycobacterium abscessus, an emerging pathogen in cystic fibrosis. M. abscessus is able to switch from a smooth (S) to a rough (R) morphotype by the loss of a surface glycopeptidolipid. R variants are associated with severe clinical forms and a 'hyper-proinflammatory' response in ex vivo and in vivo models. Using partitioning of cell surface components we found that a complex fraction, more abundant in R variants than in S variants, made a major contribution to the TLR-2-dependent hyper-proinflammatory response induced by R variants. Lipoproteins were the main TLR-2 agonists in this fraction, consistent with the larger amounts of 16 lipoproteins in cell surface extracts from R variants; 15 out of 16 being more strongly induced in R variant than in S variant. Genetic interruption of glycopeptidolipid pathway in wild-type S variant resulted in R phenotype with similar induction of lipoprotein genes. In conclusion, R morphotype in M. abscessus is associated with increased synthesis/exposure at the cell surface of lipoproteins, these changes profoundly modifying the innate immune response through TLR-2-dependent mechanisms.
- UNIVERSITE PARIS DESCARTES France
- UNIVERSITE DE TOULOUSE France
- Paul Sabatier University France
- University of Paris France
- Université de Versailles Saint-Quentin-en-Yvelines France
Fluorescent Antibody Technique, MESH: Electrophoresis, MESH: Virulence, Polymerase Chain Reaction, Mice, MESH: Glycopeptides / metabolism, MESH: Mycobacterium Infections / immunology, MESH: Animals, MESH: Lipoproteins / metabolism*, MESH: Fluorescent Antibody Technique, MESH: Mycobacterium / immunology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Virulence, Glycopeptides, MESH: Toll-Like Receptor 2 / agonists, Phenotype, MESH: HEK293 Cells, Cytokines, Electrophoresis, Polyacrylamide Gel, MESH: Mycobacterium / metabolism*, Signal Transduction, Lipoproteins, MESH: Phenotype, Mycobacterium, MESH: Cell Membrane / immunology, MESH: Mycobacterium Infections / microbiology, Animals, Humans, MESH: Cytokines / immunology, MESH: Mice, MESH: Inflammation / immunology, Inflammation, Mycobacterium Infections, MESH: Humans, Polyacrylamide Gel, Macrophages, MESH: Cytokines / metabolism, Cell Membrane, MESH: Macrophages, MESH: Polymerase Chain Reaction, MESH: Toll-Like Receptor 2 / metabolism*, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Signal Transduction*, Toll-Like Receptor 2, MESH: Mycobacterium / pathogenicity, HEK293 Cells, MESH: Cytokines / biosynthesis, MESH: Lipoproteins / immunology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Glycopeptides / immunology
Fluorescent Antibody Technique, MESH: Electrophoresis, MESH: Virulence, Polymerase Chain Reaction, Mice, MESH: Glycopeptides / metabolism, MESH: Mycobacterium Infections / immunology, MESH: Animals, MESH: Lipoproteins / metabolism*, MESH: Fluorescent Antibody Technique, MESH: Mycobacterium / immunology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Virulence, Glycopeptides, MESH: Toll-Like Receptor 2 / agonists, Phenotype, MESH: HEK293 Cells, Cytokines, Electrophoresis, Polyacrylamide Gel, MESH: Mycobacterium / metabolism*, Signal Transduction, Lipoproteins, MESH: Phenotype, Mycobacterium, MESH: Cell Membrane / immunology, MESH: Mycobacterium Infections / microbiology, Animals, Humans, MESH: Cytokines / immunology, MESH: Mice, MESH: Inflammation / immunology, Inflammation, Mycobacterium Infections, MESH: Humans, Polyacrylamide Gel, Macrophages, MESH: Cytokines / metabolism, Cell Membrane, MESH: Macrophages, MESH: Polymerase Chain Reaction, MESH: Toll-Like Receptor 2 / metabolism*, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Signal Transduction*, Toll-Like Receptor 2, MESH: Mycobacterium / pathogenicity, HEK293 Cells, MESH: Cytokines / biosynthesis, MESH: Lipoproteins / immunology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Glycopeptides / immunology
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