The cell wall provides a major physical interface between fungal pathogens and their mammalian host. This extracellular armor is critical for fungal cell homeostasis and survival. Fungus-specific cell wall moieties, such as β-1,3-glucan, are recognized as pathogen-associated molecular patterns (PAMPs) that activate immune-mediated clearance mechanisms. We have reported that the opportunistic human fungal pathogen Candida albicans masks β-1,3-glucan following exposure to lactate, hypoxia, or iron depletion. However, the precise mechanism(s) by which C. albicans masks β-1,3-glucan has remained obscure. Here, we identify a secreted exoglucanase, Xog1, that is induced in response to lactate or hypoxia. Xog1 functions downstream of the lactate-induced β-glucan “masking” pathway to promote β-1,3-glucan “shaving.” Inactivation of XOG1 blocks most but not all β-1,3-glucan masking in response to lactate, suggesting that other activities contribute to this phenomenon. Nevertheless, XOG1 deletion attenuates the lactate-induced reductions in phagocytosis and cytokine stimulation normally observed for wild-type cells. We also demonstrate that the pharmacological inhibition of exoglucanases undermines β-glucan shaving, enhances the immune visibility of the fungus, and attenuates its virulence. Our study establishes a new mechanism underlying environmentally induced PAMP remodeling that can be manipulated pharmacologically to influence immune recognition and infection outcomes.

中文翻译：

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表位剃须促进真菌免疫逃避。

细胞壁提供了真菌病原体与其哺乳动物宿主之间的主要物理界面。这种细胞外装甲对于真菌细胞的稳态和生存至关重要。真菌特异性细胞壁部分，例如 β-1,3-葡聚糖，被认为是激活免疫介导的清除机制的病原体相关分子模式 (PAMP)。我们已经报道，机会性人类真菌病原体白色念珠菌会在暴露于乳酸、缺氧或缺铁后掩盖 β-1,3-葡聚糖。然而，白色念珠菌的确切机制面罩β-1,3-葡聚糖一直不为人知。在这里，我们确定了一种分泌的外切葡聚糖酶 Xog1，它是响应乳酸或缺氧而诱导的。Xog1 在乳酸诱导的 β-葡聚糖“掩蔽”途径下游发挥作用，以促进 β-1,3-葡聚糖“剃须”。XOG1的失活阻断了大多数但不是所有 β-1,3-葡聚糖对乳酸的反应，表明其他活动有助于这种现象。尽管如此，XOG1缺失减弱了通常在野生型细胞中观察到的乳酸诱导的吞噬作用和细胞因子刺激的减少。我们还证明外切葡聚糖酶的药理抑制作用会破坏 β-葡聚糖剃须，增强真菌的免疫可见性并减弱其毒力。我们的研究建立了一种潜在的环境诱导 PAMP 重塑的新机制，可以通过药理学操作来影响免疫识别和感染结果。