Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Laboratory of Immune Regulation, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Commun Biol. 2021 Mar 16;4(1):342. doi: 10.1038/s42003-021-01870-3.
Severe infection often causes a septic cytokine storm followed by immune exhaustion/paralysis. Not surprisingly, many pathogens are equipped with various anti-inflammatory mechanisms. Such mechanisms might be leveraged clinically to control septic cytokine storms. Here we show that N-glycan from pathogenic C. albicans ameliorates mouse sepsis through immunosuppressive cytokine IL-10. In a sepsis model using lipopolysaccharide (LPS), injection of the N-glycan upregulated serum IL-10, and suppressed pro-inflammatory IL-1β, TNF-α and IFN-γ. The N-glycan also improved the survival of mice challenged by LPS. Analyses of structurally defined N-glycans from several yeast strains revealed that the mannose core is key to the upregulation of IL-10. Knocking out the C-type lectin Dectin-2 abrogated the N-glycan-mediated IL-10 augmentation. Furthermore, C. albicans N-glycan ameliorated immune exhaustion/immune paralysis after acute inflammation. Our results suggest a strategy where the immunosuppressive mechanism of one pathogen can be applied to attenuate a severe inflammation/cytokine storm caused by another pathogen.
严重感染通常会导致脓毒症细胞因子风暴，随后是免疫衰竭/麻痹。毫不奇怪，许多病原体都配备了各种抗炎机制。这些机制可能会被临床利用来控制脓毒症细胞因子风暴。在这里，我们表明，致病性白念珠菌的 N-聚糖通过免疫抑制细胞因子 IL-10 改善了小鼠脓毒症。在使用脂多糖 (LPS) 的脓毒症模型中，N-聚糖的注射上调了血清中的 IL-10，并抑制了促炎细胞因子 IL-1β、TNF-α 和 IFN-γ。N-聚糖还提高了 LPS 攻击小鼠的存活率。对来自几种酵母株的结构定义 N-聚糖的分析表明，甘露糖核心是上调 IL-10 的关键。敲除 C 型凝集素 Dectin-2 可消除 N-聚糖介导的 IL-10 扩增。此外，白念珠菌 N-聚糖改善了急性炎症后的免疫衰竭/免疫麻痹。我们的研究结果表明了一种策略，即一种病原体的免疫抑制机制可用于减轻另一种病原体引起的严重炎症/细胞因子风暴。
