Induction of nitric oxide synthase in Anopheles stephensi by Plasmodium falciparum:: Mechanism of signaling and the role of parasite glycosylphosphatidylinositols
Induction of nitric oxide synthase in Anopheles stephensi by Plasmodium falciparum:: Mechanism of signaling and the role of parasite glycosylphosphatidylinositols
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DOI：
10.1128/iai.73.5.2778-2789.2005
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发表时间：
2005-05-01
影响因子：
3.1
通讯作者：
Luckhart, S
中科院分区：
文献类型：
--
作者：
Lim, JH;Gowda, DC;Luckhart, S
疟疾寄生虫（疟原虫属）感染斯氏按蚊后，A. stephensi一氧化氮合酶（AsNOS）中肠上皮细胞早在6 h postinfection和间歇性此后。这种诱导导致充满血液的中肠中一氧化氮（NO）的炎症水平的合成，这对寄生虫的发育产生不利影响。在哺乳动物中，恶性疟原虫糖基磷脂酰肌醇（PfGPIs）可以诱导免疫和内皮细胞中的NOS表达，并足以复制寄生虫感染的主要影响。这些作用部分通过PfGPIs模拟胰岛素信号传导介导。在这项研究中，我们证明PfGPIs可以诱导A. stephensi细胞在体外和中肠上皮在体内。恶性疟原虫裂殖子和PfGPIs的信号传导通过A. stephensi Akt/蛋白激酶B和涉及DSOR 1、促分裂原活化蛋白激酶激酶和细胞外信号调节激酶的途径。然而，尽管A.在stephensi细胞中，恶性疟原虫和PfGPIs的信号传导明显不同于胰岛素的信号传导。因此，尽管PfGPIs对胰岛素的模拟似乎仅限于恶性疟原虫的哺乳动物宿主，但PfGPIs作为先天免疫的主要寄生虫来源信号的保守性现在可以扩展到包括按蚊，表明先天免疫的寄生虫信号传导在蚊子和哺乳动物细胞中是保守的。
Malaria parasite (Plasmodium spp.) infection in the mosquito Anopheles stephensi induces significant expression of A. stephensi nitric oxide synthase (AsNOS) in the midgut epithelium as early as 6 h postinfection and intermittently thereafter. This induction results in the synthesis of inflammatory levels of nitric oxide (NO) in the blood-filled midgut that adversely impact parasite development. In mammals, P. falciparum glycosylphosphatidylinositols (PfGPIs) can induce NOS expression in immune and endothelial cells and are sufficient to reproduce the major effects of parasite infection. These effects are mediated in part by mimicry of insulin signaling by PfGPIs. In this study, we demonstrate that PfGPIs can induce AsNOS expression in A. stephensi cells in vitro and in the midgut epithelium in vivo. Signaling by P. falciparum merozoites and PfGPIs is mediated through A. stephensi Akt/protein kinase B and a pathway involving DSOR1, a mitogen-activated protein kinase kinase, and an extracellular signal-regulated kinase. However, despite the involvement of kinases that are also associated with insulin signaling in A. stephensi cells, signaling by P. falciparum and by PfGPIs is distinctively different from signaling by insulin. Therefore, although mimicry of insulin by PfGPIs appears to be restricted to mammalian hosts of P. falciparum, the conservation of PfGPIs as a prominent parasite-derived signal of innate immunity can now be extended to include Anopheles mosquitoes, indicating that parasite signaling of innate immunity is conserved in mosquito and mammalian cells.