Remarkable stability in patterns of blood-stage gene expression during episodes of non-lethal Plasmodium yoelii malaria.

Remarkable stability in patterns of blood-stage gene expression during episodes of non-lethal Plasmodium yoelii malaria.
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DOI:
10.1186/1475-2875-11-265
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发表时间:
2012-08-06
期刊:
影响因子:
3
通讯作者:
Burns JM Jr
Burns JM Jr
中科院分区:
医学3区
文献类型:
--
作者:
Cernetich-Ott A;Daly TM;Vaidya AB;Bergman LW;Burns JM Jr

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使用同步的血液阶段恶性疟原虫疟疾寄生虫的体外培养物进行的微阵列研究揭示了基因表达的“及时”级联,并有一些迹象表明,即使存在外部应激源,这些转录模式也保持稳定。然而,对从感染患者血液中获得的恶性疟原虫血液阶段寄生虫的转录进行直接分析表明,寄生虫基因表达可能受到宿主体内环境中存在的因素的调节。本研究的目的是检查啮齿动物疟疾寄生虫约氏疟原虫 17X 基因表达的变化,同时改变体内复制设置。使用约氏疟原虫 17X 寄生虫在体内复制,使用约氏疟原虫 DNA 微阵列检查从个体小鼠、独立感染、寄生虫血症上升、峰值和下降期间以及存在和不存在宿主抗体反应的情况下分离的寄生虫的差异基因表达。尽管还完成了对 P. yoelii 中两个多基因家族(yir 和 pyst-a 家族)表达模式的分析,但主要重点是进行全基因组分析,以确定与特定生物途径相关的基因组的协调变化。在整个实验条件下,转录出人意料地稳定,几乎没有证据表明不同的转录状态或特定途径的一致变化。当比较由于寄生虫负载和/或宿主细胞可用性引起的差异时,差异基因表达最大。然而,差异表达基因的数量普遍较低。在差异表达的基因中,许多涉及生物学上不同的途径。 yir 和 pyst 多基因家族的成员几乎没有差异表达,这些基因编码与受感染红细胞膜相关的多态性蛋白质。然而,无论实验条件如何,这些基因在血液阶段感染期间都会表达相对大量的基因。总而言之,这些结果表明:1)约氏疟原虫基因表达在宿主环境变化的情况下保持稳定,2)大量多态性 yir 和 pyst-a 基因的同时表达,而不是响应特定宿主因素的差异表达,本身可能限制宿主免疫反应的有效性。
Microarray studies using in vitro cultures of synchronized, blood-stage Plasmodium falciparum malaria parasites have revealed a ‘just-in-time’ cascade of gene expression with some indication that these transcriptional patterns remain stable even in the presence of external stressors. However, direct analysis of transcription in P. falciparum blood-stage parasites obtained from the blood of infected patients suggests that parasite gene expression may be modulated by factors present in the in vivo environment of the host. The aim of this study was to examine changes in gene expression of the rodent malaria parasite, Plasmodium yoelii 17X, while varying the in vivo setting of replication. Using P. yoelii 17X parasites replicating in vivo, differential gene expression in parasites isolated from individual mice, from independent infections, during ascending, peak and descending parasitaemia and in the presence and absence of host antibody responses was examined using P. yoelii DNA microarrays. A genome-wide analysis to identify coordinated changes in groups of genes associated with specific biological pathways was a primary focus, although an analysis of the expression patterns of two multi-gene families in P. yoelii, the yir and pyst-a families, was also completed. Across experimental conditions, transcription was surprisingly stable with little evidence for distinct transcriptional states or for consistent changes in specific pathways. Differential gene expression was greatest when comparing differences due to parasite load and/or host cell availability. However, the number of differentially expressed genes was generally low. Of genes that were differentially expressed, many involved biologically diverse pathways. There was little to no differential expression of members of the yir and pyst-a multigene families that encode polymorphic proteins associated with the membrane of infected erythrocytes. However, a relatively large number of these genes were expressed during blood-stage infection regardless of experimental condition. Taken together, these results indicate that 1) P. yoelii gene expression remains stable in the presence of a changing host environment, and 2) concurrent expression of a large number of the polymorphic yir and pyst-a genes, rather than differential expression in response to specific host factors, may in itself limit the effectiveness of host immune responses.
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