Genome-wide transcriptome analysis of immunity related genes in the mosquito, Aedes aegypti

Three major signaling pathways of the mosquito innate immune system, including Toll, IMD, and JAK-STAT, are involved in pathogen-elicited defense responses. NF-κB factors, REL1 and REL2, are two key transcription activators of the Toll and IMD pathway, while Cactus, Caspar, and PIAS are considered to be negative regulators of the Toll, IMD, and JAK-STAT pathways, respectively. Transgenic Aedes aegypti mosquitoes, with gain-of-function REL1 (REL1+) and REL2 (REL2+) have been constructed in our previous studies. The transcriptome profiles of these two transgenic strains, together with those of Cactus, Caspar, and PIAS-depleted mosquitoes were investigated and compared by genome-wide microarray analysis. The expression level of 297 and 299 genes were significantly changed in the REL1+ and REL2+ lines respectively. Immune related genes constituted over half of the affected genes. Furthermore, REL1+, REL2+, and Cactus-depleted mosquitoes showed an overlapped regulated gene repertoire. These results confirmed the central role of REL1 and REL2 in the Toll and IMD pathways. The avian malaria parasite, Plasmodium gallinaceum elicited a very distinct repertoire of immune genes in Ae. Aegypti with REL1+, REL2+, and Cactus depleted mosquitoes. Moreover, there is considerable overlap of fat body regulated genes between PIAS-depleted and Plasmodium-infected wild-type mosquitoes. RNAi-mediated PIAS depletion activates the JAK-STAT pathway as demonstrated by the increased level of SOCS36E transcript, a component of JAK-STAT. In addition, depletion of PIAS drastically reduced the parasite proliferation in Ae. aegypti, suggesting the involvement of JAK-STAT in anti-parasite defense. Overall, results of these studies improve our understanding of the complexity of vector-parasite interactions.