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Updated: May 4, 2026
Live-cell Video Microscopy of Fungal Pathogen Phagocytosis
Published on: January 9, 2013
Deficient beta-mannosylation of Candida albicans phospholipomannan affects the proinflammatory response in
Audrey Devillers1, Flavie Courjol1, Chantal Fradin1
1Inserm U995, Team 2, Lille, France ; Université Lille Nord de France, Lille, France ; Université Droit et Santé Lille2, Lille, France.
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.
Insights
Phospholipomannan (PLM) from Candida albicans activates immune cells. Longer PLM glycan chains enhance TNF-α production and galectin-3 interaction, amplifying the inflammatory response.
Area of Science:
- Immunology
- Microbiology
- Glycobiology
Background:
- Candida albicans cell surfaces contain phospholipomannan (PLM), a glycosphingolipid shed upon host cell contact.
- PLM's glycan chains vary in length between C. albicans serotypes A and B.
- The proinflammatory potential of PLM based on its glycosylation status requires further investigation.
Purpose of the Study:
- To compare the proinflammatory activities of PLMs from C. albicans serotype A, serotype B, and a bmt6Δ mutant.
- To investigate the role of PLM glycan chain length in activating caspase-1 and cytokine production (IL-1β, TNF-α) in macrophages.
- To determine the influence of galectin-3 on PLM-induced inflammatory responses.
Main Methods:
- Purification of PLM from C. albicans serotype A, serotype B, and bmt6Δ mutant strains.
- Incubation of murine macrophage cell line J774 with purified PLMs.
- Measurement of caspase-1 activation, IL-1β and TNF-α secretion, and ROS production.
- Assessment of galectin-3 potentiation of PLM-induced TNF-α production.
Main Results:
- All tested PLMs activated caspase-1 independently of glycan chain length, with longer chains enhancing IL-1β secretion.
- PLMs did not stimulate ROS production, suggesting a ROS-independent caspase-1 activation pathway.
- Only PLM from serotype A (PLM-A) induced TNF-α production, potentiated by soluble galectin-3, and this was independent of endocytosis.
- PLMs from serotype B and the bmt6Δ mutant did not induce TNF-α production, even with galectin-3 pretreatment.
Conclusions:
- PLMs from C. albicans can induce a proinflammatory state in macrophages, partly dependent on glycosylation.
- Longer glycan chains on PLM-A favor interaction with soluble galectin-3, amplifying TNF-α production.
- These findings highlight the role of PLM glycosylation in modulating host inflammatory responses.
