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Differential MicroRNA Expression in Experimental Cerebral and Noncerebral Malaria

机译：MicroRNA在实验性脑和非脑疟疾中的差异表达。

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MicroRNAs (miRNAs) are posttranscriptional regulatory molecules that have been implicated in the regulation of immune responses, but their role in the immune response to Plasmodium infection is unknown. We studied the expression of selected miRNAs following infection of CBA mice with Plasmodium berghei ANKA (PbA), which causes cerebral malaria (CM), or Plasmodium berghei K173 (PbK), which causes severe malaria but without cerebral complications, termed non-CM. The differential expression profiles of selected miRNAs (let-7i, miR-27a, miR-150, miR-126, miR-210, and miR-155) were analyzed in mouse brain and heart tissue by quantitative reverse transcription-PCR (qRT-PCR). We identified three miRNAs that were differentially expressed in the brain of PbA-infected CBA mice: let7i, miR-27a, and miR-150. In contrast, no miRNA changes were detected in the heart, an organ with no known pathology during acute malaria. To investigate the involvement of let-7i, miR-27a, and miR-150 in CM-resistant mice, we assessed the expression levels in gamma interferon knockout (IFN-γ?/?) mice on a C57BL/6 genetic background. The expression of let-7i, miR-27a, and miR-150 was unchanged in both wild-type (WT) and IFN-γ?/? mice following infection. Overexpression of these three miRNAs during PbA, but not PbK, infection in WT mice may be critical for the triggering of the neurological syndrome via regulation of their potential downstream targets. Our data suggest that in the CBA mouse at least, miRNA may have a regulatory role in the pathogenesis of severe malaria.
机译：MicroRNA（miRNA）是转录后的调控分子，与免疫反应的调控有关，但在疟原虫感染的免疫反应中的作用尚不清楚。我们研究了CBA小鼠感染伯氏疟原虫ANKA（PbA）导致脑部疟疾（CM）或伯氏疟原虫K173（PbK）引起严重疟疾但无脑并发症（称为非CM）后，选定miRNA的表达。通过定量逆转录PCR（qRT-PCR）分析了选定的miRNA（let-7i，miR-27a，miR-150，miR-126，miR-210和miR-155）的差异表达谱PCR）。我们鉴定了三种在PbA感染的CBA小鼠的大脑中差异表达的miRNA：let7i，miR-27a和miR-150。相反，在急性疟疾期间没有已知病理的器官心脏中未检测到miRNA变化。为了调查let-7i，miR-27a和miR-150在抗CM小鼠中的参与，我们评估了γ-干扰素敲除（IFN-γ？/？）小鼠在γ-干扰素小鼠中的表达水平。 C57BL / 6遗传背景。感染后，野生型（WT）和IFN-γα/β小鼠中let-7i，miR-27a和miR-150的表达均未改变。 WT小鼠在PbA感染期间而不是PbK感染期间这三种miRNA的过表达可能通过调节其潜在的下游靶点而触发神经系统综合症。我们的数据表明，至少在CBA小鼠中，miRNA可能在严重疟疾的发病机理中具有调节作用。

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