title: Lipoglycans contribute to innate immune detection of mycobacteria.
abstract: Innate immune recognition is based on the detection, by pattern recognition receptors (PRRs), of molecular structures that are unique to microorganisms. Lipoglycans are macromolecules specific to the cell envelope of mycobacteria and related genera. They have been described to be ligands, as purified molecules, of several PRRs, including the C-type lectins Mannose Receptor and DC-SIGN, as well as TLR2. However, whether they are really sensed by these receptors in the context of a bacterium infection remains unclear. To address this question, we used the model organism Mycobacterium smegmatis to generate mutants altered for the production of lipoglycans. Since their biosynthesis cannot be fully abrogated, we manipulated the biosynthesis pathway of GDP-Mannose to obtain some strains with either augmented (∼1.7 fold) or reduced (∼2 fold) production of lipoglycans. Interestingly, infection experiments demonstrated a direct correlation between the amount of lipoglycans in the bacterial cell envelope on one hand and the magnitude of innate immune signaling in TLR2 reporter cells, monocyte/macrophage THP-1 cell line and human dendritic cells, as revealed by NF-κB activation and IL-8 production, on the other hand. These data establish that lipoglycans are bona fide Microbe-Associated Molecular Patterns contributing to innate immune detection of mycobacteria, via TLR2 among other PRRs.
authors.affiliation: CNRS, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France.
authors.forename: Shyam
authors.initials: S
authors.lastname: Krishna
authors.forename: Aurélie
authors.initials: A
authors.lastname: Ray
authors.forename: Shiv K
authors.initials: SK
authors.lastname: Dubey
authors.forename: Gérald
authors.initials: G
authors.lastname: Larrouy-Maumus
authors.forename: Christian
authors.initials: C
authors.lastname: Chalut
authors.forename: Romain
authors.initials: R
authors.lastname: Castanier
authors.forename: Audrey
authors.initials: A
authors.lastname: Noguera
authors.forename: Martine
authors.initials: M
authors.lastname: Gilleron
authors.forename: Germain
authors.initials: G
authors.lastname: Puzo
authors.forename: Alain
authors.initials: A
authors.lastname: Vercellone
authors.forename: K Madhavan
authors.initials: KM
authors.lastname: Nampoothiri
authors.forename: Jérôme
authors.initials: J
authors.lastname: Nigou
mesh_terms: D002241:Carbohydrates / Q000737:chemistry; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology; D004591:Electrophoresis, Polyacrylamide Gel; D006153:Guanosine Diphosphate / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry*; D008358:Mannose / Q000737:chemistry; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D020102:Mycobacterium smegmatis / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D002241:Carbohydrates; D015815:Cell Adhesion Molecules; D006153:Guanosine Diphosphate; D016209:Interleukin-8; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008358:Mannose; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin