Boosting NF-κB-dependent basal immunity of Anopheles gambiae aborts development of Plasmodium berghei
Boosting NF-κB-dependent basal immunity of Anopheles gambiae aborts development of Plasmodium berghei
复制标题
DOI：
10.1016/j.immuni.2006.08.019
复制
发表时间：
2006-10-01
期刊：
影响因子：
32.4
通讯作者：
Levashina, Elena A.
中科院分区：
文献类型：
--
作者：
Frolet, Cecile;Thoma, Martine;Levashina, Elena A.
冈比亚按蚊是原生动物疟疾寄生虫恶性疟原虫的主要媒介，它能产生强大的抗寄生虫反应，在中肠入侵期间导致显著的寄生虫损失。在这里，我们证明了这些抗寄生虫防御由入侵前和入侵后阶段组成，入侵前阶段主要受核因子-kappa B转录因子Rel1和Rel2成员的调控。同时沉默Rel1和Rel2降低了主要抗寄生虫基因TEP1和LRIM1的基础表达，并取消了按蚊对啮齿动物疟疾寄生虫P.berghel的抗性。相反，在感染前耗尽Rel1的负调控因子仙人掌，可以增强TEP1和其他免疫因子的基础表达，并完全阻止寄生虫的发展。我们的发现揭示了入侵前防御在消灭寄生虫方面的关键作用，这至少部分是基于循环血液分子。
Anopheles gambiae, the major vector for the protozoan malaria parasite Plasmodium falciparum, mounts powerful antiparasitic responses that cause marked parasite loss during midgut invasion. Here, we showed that these antiparasitic defenses were composed of pre- and postinvasion phases and that the preinvasion phase was predominantly regulated by Rel1 and Rel2 members of the NF-kappa B transcription factors. Concurrent silencing of Rel1 and Rel2 decreased the basal expression of the major antiparasitic genes TEP1 and LRIM1 and abolished resistance of Anopheles to the rodent malaria parasite P. berghel. Conversely, depletion of a negative regulator of Rel1, Cactus, prior to infection, enhanced the basal expression of TEP1 and of other immune factors and completely prevented parasite development. Our findings uncover the crucial role of the preinvasion defense in the elimination of parasites, which is at least in part based on circulating blood molecules.