Frolet Cécile, Thoma Martine, Blandin Stéphanie, Hoffmann Jules A, Levashina Elena A
Institut de Biologie Moléculaire et Cellulaire, UPR9022 du CNRS, Equipe Avenir - Inserm, 15 rue R. Descartes, 67084 Strasbourg Cedex, France.
Immunity. 2006 Oct;25(4):677-85. doi: 10.1016/j.immuni.2006.08.019.
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-kappaB 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. berghei. 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.
冈比亚按蚊是原生动物疟原虫恶性疟原虫的主要传播媒介，它会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，我们表明这些抗寄生虫防御由入侵前和入侵后阶段组成，并且入侵前阶段主要由NF-κB转录因子的Rel1和Rel2成员调节。Rel1和Rel2的同时沉默降低了主要抗寄生虫基因TEP1和LRIM1的基础表达，并消除了按蚊对啮齿动物疟原虫伯氏疟原虫的抗性。相反，在感染前耗尽Rel1的负调节因子Cactus，增强了TEP1和其他免疫因子的基础表达，并完全阻止了寄生虫的发育。我们的研究结果揭示了入侵前防御在消除寄生虫中的关键作用，这至少部分基于循环血液分子。
