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首页> 外文期刊>The journal of clinical investigation >Ab binding alters gene expression in Cryptococcus neoformans and directly modulates fungal metabolism
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Ab binding alters gene expression in Cryptococcus neoformans and directly modulates fungal metabolism

机译:抗体结合改变新隐球菌的基因表达并直接调节真菌代谢

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Abs facilitate humoral immunity via the classical mechanisms of opsonization, complement activation, Ab-dependent cellular cytotoxicity, and toxin/viral neutralization. There is also evidence that some Abs mediate direct antimicrobial effects. For example, Ab binding to the polysaccharide capsule of the human pathogenic fungus Cryptococcus neoformans promotes opsonization but also inhibits polysaccharide release and biofilm formation. To investigate whether Ab binding affects C. neoformans directly, we analyzed fungal gene expression after binding of protective and nonprotective mAbs. The 2 IgM Abs and 1 IgG1 Ab tested each induced different changes in gene expression. The protective IgG1 mAb upregulated genes encoding proteins involved in fatty acid synthesis, the protective IgM mAb downregulated genes encoding proteins required for protein translation, and the nonprotective IgM mAb had modest effects on gene expression. Differences in gene expression correlated with mAb binding to different locations of the capsule. Of the 3 Abs tested, the protective IgG1 mAb bound to C. neoformans closest to the cell wall, produced specific differences in the pattern of phosphorylated proteins, caused changes in lipid metabolism, and resulted in increased susceptibility to the antifungal drug amphotericin B. These results suggest what we believe to be a new mode of action for Ab-mediated immunity and raise the possibility that immunoglobulins mediate cross talk between microbes and hosts through their effects on microbial metabolism.
机译:Abs通过调理作用,补体激活,Ab依赖性细胞毒性和毒素/病毒中和的经典机制促进体液免疫。也有证据表明,某些Abs可直接发挥抗菌作用。例如,与人病原性真菌新隐球菌的多糖荚膜结合的Ab促进调理作用,但也抑制多糖释放和生物膜形成。为了调查Ab结合是否直接影响新孢子虫,我们分析了保护性和非保护性mAb结合后的真菌基因表达。测试的2个IgM Abs和1个IgG1 Ab分别引起基因表达的不同变化。保护性IgG1 mAb基因上调编码与脂肪酸合成有关的蛋白质,保护性IgM mAb基因下调编码蛋白质翻译所需蛋白质的蛋白,以及非保护性IgM mAb对基因表达的影响很小。基因表达的差异与mAb结合到胶囊的不同位置有关。在测试的3种Abs中,与最靠近细胞壁的新孢梭菌结合的保护性IgG1 mAb在磷酸化蛋白的模式上产生特定差异,导致脂质代谢发生变化,并导致对抗真菌药两性霉素B的敏感性增加。结果表明,我们认为这是Ab介导的免疫的新作用方式,并提高了免疫球蛋白通过其对微生物代谢的影响来介导微生物与宿主之间串扰的可能性。

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