Miu Jenny, Hunt Nicholas H, Ball Helen J
Molecular Immunopathology Unit, Bosch Institute, Medical Foundation Building (K25), University of Sydney, Sydney, New South Wales 2006, Australia.
Infect Immun. 2008 May;76(5):1812-24. doi: 10.1128/IAI.01650-07. Epub 2008 Feb 25.
Cerebral malaria (CM) can be a fatal manifestation of Plasmodium falciparum infection. We examined global gene expression patterns during fatal murine CM (FMCM) and noncerebral malaria (NCM) by microarray analysis. There was differential expression of a number of genes, including some not yet characterized in the pathogenesis of FMCM. Some gene induction was observed during Plasmodium berghei infection regardless of the development of CM, and there was a predominance of genes linked to interferon responses, even in NCM. However, upon real-time PCR validation and quantitation, these genes were much more highly expressed in FMCM than in NCM. The observed changes included genes belonging to pathways such as interferon signaling, major histocompatibility complex processing and presentation, apoptosis, and immunomodulatory and antimicrobial processes. We further characterized differentially expressed genes by examining the cellular source of their expression as well as their temporal expression patterns during the course of malaria infection. These data identify a number of novel genes that represent interesting candidates for further investigation in FMCM.
脑型疟疾(CM)可能是恶性疟原虫感染的一种致命表现形式。我们通过微阵列分析研究了致死性小鼠脑型疟疾(FMCM)和非脑型疟疾(NCM)期间的全球基因表达模式。有许多基因存在差异表达,包括一些在FMCM发病机制中尚未明确特征的基因。在伯氏疟原虫感染期间,无论CM是否发生,均观察到一些基因的诱导,并且即使在NCM中,与干扰素反应相关的基因也占主导地位。然而,经实时PCR验证和定量分析,这些基因在FMCM中的表达水平远高于NCM。观察到的变化包括属于干扰素信号传导、主要组织相容性复合体加工和呈递、细胞凋亡以及免疫调节和抗菌过程等途径的基因。我们通过检查其表达的细胞来源以及疟疾感染过程中的时间表达模式,进一步对差异表达基因进行了表征。这些数据确定了一些新基因,它们是FMCM中进一步研究的有趣候选基因。