Ingestion of hemozoin by peripheral blood mononuclear cells alters temporal gene expression of ubiquitination processes.
Ingestion of hemozoin by peripheral blood mononuclear cells alters temporal gene expression of ubiquitination processes.
复制标题
外周血单核细胞摄入血元量会改变泛素化过程的时间基因表达。
DOI：
10.1016/j.bbrep.2022.101207
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发表时间：
2022-03
影响因子：
2.7
通讯作者：
Perkins DJ
中科院分区：
文献类型：
--
作者：
Anyona SB;Cheng Q;Raballah E;Hurwitz I;Lambert CG;McMahon BH;Ouma C;Perkins DJ
恶性疟原虫（Pf）疟疾是全世界儿童发病率和死亡率的主要原因之一。在自然感染期间，循环吞噬细胞摄取疟原虫产物疟原虫色素（PfHz）诱导先天免疫失调并增强疟疾发病机制。用生理浓度的PfHz处理来自健康、未患疟疾的供体的培养的外周血单核细胞（PBMC）可以作为研究细胞过程的体外模型。虽然宿主泛素化过程的中断是许多疾病发病机制的核心，但该系统在疟疾中仍未被探索。因此，我们研究了PfHz对参与泛素化过程的84个基因的时间表达模式的影响。在不存在或存在PfHz的情况下培养供体PBMC 3、9和24小时。用PfHz刺激3小时没有显著改变基因表达。然而，孵育9 h引起6个基因的显著变化：4个下调（FBXO 4、NEDD 8、UBE 2E3和UBE 2W），2个上调（HERC5和UBE 2J1）。PfHz处理24 h显著改变了14个基因的表达：12个下调（ANAPC11，BRCC 3，CUL4B，FBXO 4，MIB1，SKP2，TP53，UBA 2，UBA 3，UBE 2G1，UBE 2G2和WWP1），而2个上调（UBE 2J1和UBE 2Z）。总的来说，这些结果表明，吞噬PfHz的PBMC eleventh时间的变化，在转录谱的基因中央主机泛素化过程。这里提出的结果表明，在泛素化的中断可能是一个以前未发现的疟疾发病机制的特点。PBMC对PfHz的吞噬作用是一种可行的重症疟疾体外模型。在PfHz处理的PBMC中观察到泛素化过程基因的mRNA表达改变。在孵育后9小时和24小时观察到PfHz刺激的PBMC中的基因表达。6个和14个泛素化基因分别在9和24 h差异表达。泛素化过程中断是重症疟疾的病理生理学机制。
Plasmodium falciparum (Pf) malaria is among the leading causes of childhood morbidity and mortality worldwide. During a natural infection, ingestion of the malarial parasite product, hemozoin (PfHz), by circulating phagocytic cells induces dysregulation in innate immunity and enhances malaria pathogenesis. Treatment of cultured peripheral blood mononuclear cells (PBMCs) from healthy, malaria-naïve donors with physiological concentrations of PfHz can serve as an in vitro model to investigate cellular processes. Although disruptions in host ubiquitination processes are central to the pathogenesis of many diseases, this system remains unexplored in malaria. As such, we investigated the impact of PfHz on the temporal expression patterns of 84 genes involved in ubiquitination processes. Donor PBMCs were cultured in the absence or presence of PfHz for 3-, 9-, and 24 h. Stimulation with PfHz for 3 h did not significantly alter gene expression. Incubation for 9 h, however, elicited significant changes for 6 genes: 4 were down-regulated (FBXO4, NEDD8, UBE2E3, and UBE2W) and 2 were up-regulated (HERC5 and UBE2J1). PfHz treatment for 24 h significantly altered expression for 14 genes: 12 were down-regulated (ANAPC11, BRCC3, CUL4B, FBXO4, MIB1, SKP2, TP53, UBA2, UBA3, UBE2G1, UBE2G2, and WWP1), while 2 were up-regulated (UBE2J1 and UBE2Z). Collectively, these results demonstrate that phagocytosis of PfHz by PBMCs elicits temporal changes in the transcriptional profiles of genes central to host ubiquitination processes. Results presented here suggest that disruptions in ubiquitination may be a previously undiscovered feature of malaria pathogenesis. Phagocytosis of PfHz by PBMCs a viable in vitro model for severe malaria. Altered mRNA expression of ubiquitination process genes seen in PfHz-treated PBMCs. Gene expression in PfHz-stimulated PBMCs observed at 9 and 24 h post incubation. 6 and 14 ubiquitination genes differentially expressed at 9 and 24 h, respectively. Disrupted ubiquitination process, a pathophysiological mechanism for severe malaria.
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Liu Y;Koyutürk M;Barnholtz-Sloan JS;Chance MR
通讯作者：
Chance MR
影响因子：
11.1
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3.1
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通讯作者：
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