Plant Hormone Salicylic Acid Produced by a Malaria Parasite Controls Host Immunity and Cerebral Malaria Outcome.
Plant Hormone Salicylic Acid Produced by a Malaria Parasite Controls Host Immunity and Cerebral Malaria Outcome.
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DOI：
10.1371/journal.pone.0140559
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Nagamune K
中科院分区：
文献类型：
--
作者：
Matsubara R;Aonuma H;Kojima M;Tahara M;Andrabi SB;Sakakibara H;Nagamune K
顶复门寄生虫弓形虫产生植物激素脱落酸，但尚不清楚植物激素是否是由该门最重要的寄生虫疟疾寄生虫疟原虫产生。在这里，我们报告在伯氏疟原虫 ANKA 和弓形虫细胞裂解物中检测到水杨酸，这是一种与陆地植物免疫相关的植物激素。然而，向恶性疟原虫和弓形虫培养物中添加水杨酸没有效果。我们用 nahG 基因转染恶性疟原虫 3D7，该基因编码从感染植物的假单胞菌中分离出的水杨酸降解酶，并建立了水杨酸缺陷突变体。该突变体的寄生虫合成的前列腺素 E2 浓度显着降低，前列腺素 E2 可能作为疟原虫属的适应性进化来调节宿主免疫。为了研究水杨酸和前列腺素E2对宿主免疫的功能，我们建立了表达nahG的伯氏疟原虫ANKA突变体。通过伊文思蓝渗漏和脑组织学观察评估，感染 nahG 转染子的 C57BL/6 小鼠出现脑型疟疾增强。 nahG转染子还显着增加了小鼠的死亡率。前列腺素 E2 通过诱导 T 辅助细胞 2 细胞因子减轻脑部症状。正如预期的那样，nahG 转染子感染后，T helper-1 细胞因子（包括干扰素-γ 和白介素-2）显着升高。因此，疟原虫属的水杨酸。可能是这种威胁寄生虫的新致病因素，并可能通过寄生虫产生的前列腺素 E2 调节免疫功能。
The apicomplexan parasite Toxoplasma gondii produces the plant hormone abscisic acid, but it is unclear if phytohormones are produced by the malaria parasite Plasmodium spp., the most important parasite of this phylum. Here, we report detection of salicylic acid, an immune-related phytohormone of land plants, in P. berghei ANKA and T. gondii cell lysates. However, addition of salicylic acid to P. falciparum and T. gondii culture had no effect. We transfected P. falciparum 3D7 with the nahG gene, which encodes a salicylic acid-degrading enzyme isolated from plant-infecting Pseudomonas sp., and established a salicylic acid-deficient mutant. The mutant had a significantly decreased concentration of parasite-synthesized prostaglandin E2, which potentially modulates host immunity as an adaptive evolution of Plasmodium spp. To investigate the function of salicylic acid and prostaglandin E2 on host immunity, we established P. berghei ANKA mutants expressing nahG. C57BL/6 mice infected with nahG transfectants developed enhanced cerebral malaria, as assessed by Evans blue leakage and brain histological observation. The nahG-transfectant also significantly increased the mortality rate of mice. Prostaglandin E2 reduced the brain symptoms by induction of T helper-2 cytokines. As expected, T helper-1 cytokines including interferon-γ and interleukin-2 were significantly elevated by infection with the nahG transfectant. Thus, salicylic acid of Plasmodium spp. may be a new pathogenic factor of this threatening parasite and may modulate immune function via parasite-produced prostaglandin E2.