title: Deficient beta-mannosylation of Candida albicans phospholipomannan affects the proinflammatory response in macrophages.
abstract: Candida albicans produces a complex glycosphingolipid called phospholipomannan (PLM), which is present on the cell-wall surface of yeast and shed upon contact with host cells. The glycan moiety of PLM is composed of β-mannosides with degrees of polymerization up to 19 in C. albicans serotype A. PLM from serotype B strains displays a twofold decrease in the length of the glycan chains. In this study we compared the proinflammatory activities of PLMs purified from C. albicans serotype A and serotype B strains and from a bmt6Δ mutant of C. albicans, whose PLM is composed of short truncated oligomannosidic chain. We found that PLMs activate caspase-1 in murine macrophage cell line J774 independent of the glycan chain length although IL-1β secretion is more intense with long glycan chain. None of the tested PLMs stimulate ROS production, indicating that caspase-1 activation may occur through a ROS-independent pathway. On the other hand, only long-chain oligomannosides present on PLM from serotype A strain (PLM-A) are able to induce TNF-α production in macrophages, a property that is not affect by blocking endocytosis through latrunculin A treatment. Finally, we demonstrate that soluble and not cell surface-bound galectin-3, is able to potentiate PLM-A-induced TNF-α production in macrophages. PLMs from C. albicans serotype B and from bmt6∆ mutant are not able to induce TNF-α production and galectin-3 pretreatment does not interfere with this result. In conclusion, we show here that PLMs are able to evoke a proinflammatory state in macrophage, which is in part dependent on their glycosylation status. Long-glycan chains favor interaction with soluble galectin-3 and help amplify inflammatory response.
authors.affiliation: Inserm U995, Team 2, Lille, France ; Université Lille Nord de France, Lille, France ; Université Droit et Santé Lille2, Lille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Devillers
authors.affiliation: Inserm U995, Team 2, Lille, France ; Université Lille Nord de France, Lille, France ; Université Droit et Santé Lille2, Lille, France.
authors.forename: Flavie
authors.initials: F
authors.lastname: Courjol
authors.affiliation: Inserm U995, Team 2, Lille, France ; Université Lille Nord de France, Lille, France ; Université Droit et Santé Lille2, Lille, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Fradin
authors.affiliation: Unité Mixte de Recherche MD3, EA2405 Polarisation des macrophages et recepteurs nucleaires dans les pathologies inflammatoires et infectieuses, Université Paul Sabatier, Toulouse, France ; Unité mixte de recherche 152, Université Paul Sabatier, Toulouse, France.
authors.forename: Agnes
authors.initials: A
authors.lastname: Coste
authors.affiliation: Inserm U995, Team 2, Lille, France ; Université Lille Nord de France, Lille, France ; Université Droit et Santé Lille2, Lille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Poulain
authors.affiliation: Unité Mixte de Recherche MD3, EA2405 Polarisation des macrophages et recepteurs nucleaires dans les pathologies inflammatoires et infectieuses, Université Paul Sabatier, Toulouse, France ; Unité mixte de recherche 152, Université Paul Sabatier, Toulouse, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Pipy
authors.affiliation: Cancer Institute of the State of São Paulo, São Paulo, Brazil.
authors.forename: Emerson Soares
authors.initials: ES
authors.lastname: Bernardes
authors.affiliation: Inserm U995, Team 2, Lille, France ; Université Lille Nord de France, Lille, France ; Université Droit et Santé Lille2, Lille, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Jouault
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002176:Candida albicans / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D004586:Electrophoresis / Q000379:methods; D037502:Galectin 3 / Q000378:metabolism; D006017:Glycolipids / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D058105:Polymerization; D017382:Reactive Oxygen Species / Q000378:metabolism; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D044902:beta-Mannosidase / Q000378:metabolism*
chemical_list: D037502:Galectin 3; D006017:Glycolipids; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C400188:phospholipomannan; D044902:beta-Mannosidase; D020170:Caspase 1