CCR6 expression reduces mouse survival upon malarial challenge with Plasmodium berghei NK65 strain

BACKGROUND It has been demonstrated that proteins expressed by liver-stage Plasmodium parasites can inhibit the translocation of transcription factors to the nucleus of different cells. This process would hinder the expression of immune genes, such as the CCL20 chemokine. OBJECTIVE Since CCR6 is the only cognate receptor for CCL20, we investigated the importance of this chemokine-receptor axis against rodent malaria. METHODS CCR6-deficient (KO) and wild-type (WT) C57BL/6 mice were challenged with Plasmodium berghei (Pb) NK65 sporozoites or infected red blood cells (iRBCs). Liver parasitic cDNA, parasitemia and serum cytokine concentrations were respectively evaluated through reverse transcription-polymerase chain reaction (RT-PCR), staining thin-blood smears with Giemsa solution, and enzyme-linked immunosorbent assay (ELISA). FINDINGS Although the sporozoite challenges yielded similar liver parasitic cDNA and parasitemia, KO mice presented a prolonged survival than WT mice. After iRBC challenges, KO mice kept displaying higher survival rates as well as a decreased IL-12 p70 concentration in the serum than WT mice. CONCLUSION Our data suggest that malaria triggered by PbNK65 liver- or blood-stage forms elicit a pro-inflammatory environment that culminates with a decreased survival of infected C57BL/6 mice.

背景 已有研究证实，肝期疟原虫（liver-stage Plasmodium parasites）表达的蛋白可抑制转录因子（transcription factors）向不同细胞的细胞核转位，该过程会阻碍包括趋化因子CCL20（CCL20 chemokine）在内的免疫基因的表达。
研究目的 鉴于CCR6是CCL20的唯一同源受体，本研究探究了该趋化因子-受体轴在抗啮齿类疟疾（rodent malaria）中的作用重要性。
方法 本研究分别用伯氏疟原虫NK65（Plasmodium berghei (Pb) NK65）子孢子或感染红细胞（iRBCs）感染攻击CCR6缺陷型（KO）与野生型（WT）C57BL/6小鼠。通过逆转录聚合酶链反应（RT-PCR，reverse transcription-polymerase chain reaction）、姬姆萨染色薄血膜法及酶联免疫吸附试验（ELISA，enzyme-linked immunosorbent assay），分别检测肝期寄生虫cDNA、虫血症水平与血清细胞因子浓度。
结果 尽管子孢子感染攻击组的肝期寄生虫cDNA水平与虫血症水平无显著差异，但CCR6缺陷型小鼠的存活时长较野生型小鼠更长。在感染红细胞感染攻击组中，缺陷型小鼠同样展现出更高的存活率，且血清中IL-12 p70的浓度低于野生型小鼠。
结论 本研究数据表明，由PbNK65肝期或血液期虫体引发的疟疾会促发促炎环境，最终导致感染的C57BL/6小鼠存活率下降。