Department of Entomology and the Institute for Integrative Genome Biology, University of California, Riverside, California, United States of America.
PLoS Pathog. 2011 Nov;7(11):e1002394. doi: 10.1371/journal.ppat.1002394. Epub 2011 Nov 17.
The mosquito immune system is involved in pathogen-elicited defense responses. The NF-κB factors REL1 and REL2 are downstream transcription activators of Toll and IMD immune pathways, respectively. We have used genome-wide microarray analyses to characterize fat-body-specific gene transcript repertoires activated by either REL1 or REL2 in two transgenic strains of the mosquito Aedes aegypti. Vitellogenin gene promoter was used in each transgenic strain to ectopically express either REL1 (REL1+) or REL2 (REL2+) in a sex, tissue, and stage specific manner. There was a significant change in the transcript abundance of 297 (79 up- and 218 down-regulated) and 299 (123 up- and 176 down-regulated) genes in fat bodies of REL1+ and REL2+, respectively. Over half of the induced genes had predicted functions in immunity, and a large group of these was co-regulated by REL1 and REL2. By generating a hybrid transgenic strain, which ectopically expresses both REL1 and REL2, we have shown a synergistic action of these NF-κB factors in activating immune genes. The REL1+ immune transcriptome showed a significant overlap with that of cactus (RNAi)-depleted mosquitoes (50%). In contrast, the REL2+ -regulated transcriptome differed from the relatively small group of gene transcripts regulated by RNAi depletion of a putative inhibitor of the IMD pathway, caspar (35 up- and 140 down-regulated), suggesting that caspar contributes to regulation of a subset of IMD-pathway controlled genes. Infections of the wild type Ae. aegypti with Plasmodium gallinaceum elicited the transcription of a distinct subset of immune genes (76 up- and 25 down-regulated) relative to that observed in REL1+ and REL2+ mosquitoes. Considerable overlap was observed between the fat body transcriptome of Plasmodium-infected mosquitoes and that of mosquitoes with transiently depleted PIAS, an inhibitor of the JAK-STAT pathway. PIAS gene silencing reduced Plasmodium proliferation in Ae. aegypti, indicating the involvement of the JAK-STAT pathway in anti-Plasmodium defense in this infection model.
蚊子的免疫系统参与了病原体引发的防御反应。NF-κB 因子 REL1 和 REL2 分别是 Toll 和 IMD 免疫途径的下游转录激活因子。我们使用全基因组微阵列分析来描述在两种转基因埃及伊蚊（Aedes aegypti）品系中，脂肪体中特定基因转录本的组成，这些基因被 REL1 或 REL2 激活。在每种转基因品系中，均使用卵黄蛋白原基因启动子异位表达 REL1（REL1+）或 REL2（REL2+），具有性别、组织和阶段特异性。在 REL1+和 REL2+的脂肪体中，有 297 个（79 个上调和 218 个下调）和 299 个（123 个上调和 176 个下调）基因的转录丰度发生了显著变化。诱导基因的一半以上具有免疫预测功能，其中很大一部分受 REL1 和 REL2 共同调控。通过产生一种异位表达 REL1 和 REL2 的杂交转基因品系，我们已经证明这些 NF-κB 因子在激活免疫基因方面具有协同作用。REL1+的免疫转录组与 cactus（RNAi）耗尽的蚊子有显著重叠（50%）。相比之下，REL2+调节的转录组与 IMD 途径的一种假定抑制剂 caspar（35 个上调和 140 个下调）的 RNAi 耗尽引起的基因转录组差异较大，这表明 caspar 有助于调节 IMD 途径控制的基因的一个亚群。与 REL1+和 REL2+蚊子相比，野生型埃及伊蚊感染疟原虫引起了一组不同的免疫基因的转录（76 个上调和 25 个下调）。在感染 Plasmodium 的蚊子的脂肪体转录组与瞬时耗尽 JAK-STAT 途径抑制剂 PIAS 的蚊子的转录组之间观察到相当大的重叠。PIAS 基因沉默减少了埃及伊蚊中的疟原虫增殖，表明 JAK-STAT 途径参与了该感染模型中的抗疟原虫防御。
