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.

Highlights

  • Candida albicans produces a complex glycosphingolipid (GSL) called phospholipomannan (PLM) [1], which is present at the surface of the cell wall and is shed in contact with host cells [2,3,4,5]

  • The present study was undertaken to examine the role of the glycan moiety of PLM, a glycolipid present in the cell-wall and that plays an important role in the interplay between C. albicans and host immune cells [4,6,7,9]

  • Through a series of experiments, we demonstrated that differential glycosylation of PLM from serotype A strain (PLM-A), PLM from serotype B (PLM-B) and PLM-BMT6∆ does not affect their capacity to induce caspase-1 activation in murine macrophage-like cell line J774

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Summary

Introduction

Candida albicans produces a complex glycosphingolipid (GSL) called phospholipomannan (PLM) [1], which is present at the surface of the cell wall and is shed in contact with host cells [2,3,4,5]. PLM induces tumor necrosis factor alpha (TNF-α) secretion from cells of macrophage lineage via a TLR-2dependent pathway [6,7] and macrophage apoptosis via modulation of the ERK pathway [8,9] induced at the time of phagocytosis. The glycan moiety of PLM is unique. It is mainly composed of β-1,2 mannosides with degrees of polymerization up to 19 in C. albicans serotype A strains. Due to the prominent cell surface expression of β-1,2 mannosides in C. albicans, galectin-3 is able to discriminate between this pathogen [12]

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