Deficient beta-mannosylation of Candida albicans phospholipomannan affects the proinflammatory response in macrophages.

PLoS One 2013 19;8(12):e84771. Epub 2013 Dec 19.

Inserm U995, Team 2, Lille, France ; Université Lille Nord de France, Lille, France ; Université Droit et Santé Lille2, Lille, France.

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.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084771PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868656PMC
July 2014
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(Supplied by CrossRef)
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The Candida albicans phospholipomannan induces in vitro production of tumour necrosis factor-alpha from human and murine macrophages
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Immunology 1994
Role of extracellular signal-regulated protein kinase cascade in macrophage killing of Candida albicans
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