Inserm U995, Team 2, Lille, France ; Université Lille Nord de France, Lille, France ; Université Droit et Santé Lille2, Lille, France.
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.
PLoS One. 2013 Dec 19;8(12):e84771. doi: 10.1371/journal.pone.0084771. eCollection 2013.
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.
白色念珠菌产生一种复杂的糖脂，称为磷脂甘露聚糖（PLM），存在于酵母细胞壁表面，与宿主细胞接触时会脱落。PLM 的聚糖部分由β-甘露糖苷组成，在白色念珠菌血清型 A 中聚合度高达 19。血清型 B 菌株的 PLM 显示聚糖链长度减少了一倍。在这项研究中，我们比较了从白色念珠菌血清型 A 和 B 菌株以及白色念珠菌 bmt6Δ 突变体中纯化的 PLM 的促炎活性，该突变体的 PLM 由短的截断寡甘露糖链组成。我们发现，PLM 能够在不依赖于聚糖链长度的情况下激活鼠巨噬细胞系 J774 中的半胱天冬酶-1，尽管具有长聚糖链时 IL-1β 分泌更强烈。测试的 PLM 均不能刺激 ROS 产生，表明半胱天冬酶-1 的激活可能通过 ROS 非依赖性途径发生。另一方面，只有存在于血清型 A 菌株 PLM（PLM-A）上的长链寡甘露糖才能诱导巨噬细胞中 TNF-α 的产生，而 latrunculin A 处理阻断内吞作用不会影响这一特性。最后，我们证明了可溶性而不是细胞表面结合的半乳糖凝集素-3 能够增强巨噬细胞中 PLM-A 诱导的 TNF-α 产生。血清型 B 和 bmt6∆ 突变体的 PLM 不能诱导 TNF-α 的产生，而半乳糖凝集素-3 预处理不会干扰这一结果。总之，我们在这里表明，PLM 能够在巨噬细胞中引发促炎状态，这在一定程度上取决于它们的糖基化状态。长聚糖链有利于与可溶性半乳糖凝集素-3 相互作用，并有助于放大炎症反应。
