Dual RNA-seq of parasite and host reveals gene expression dynamics during filarial worm-mosquito interactions

Parasite biology, by its very nature, cannot be understood without integrating it with that of the host, nor can the host response be adequately explained without considering the activity of the parasite. However, due to experimental limitations, molecular studies of parasite-host systems have been predominantly one-sided investigations focusing on either of the partners. Here we conduct a joint dual RNA-seq time course analysis of filarial parasite and host mosquito to better understand the parasite processes underlying development in, and interaction with, the host tissue from the establishment of infection to the emergence of infective-stage larva. Using the Brugia malayi-Aedes aegypti system, we report the parasite gene transcription dynamics, which exhibit a highly ordered developmental program consisting of a series of cyclical and state-transitioning temporal patterns. And, we contextualize these parasite data in relation to the concurrent dynamics of the host transcriptome. Comparative analyses using uninfected tissues and different host strains reveal the influence of parasite development on the host gene transcription as well as the influence of host environment on the parasite gene transcription. Furthermore, we critically evaluate the life-cycle transcriptome of B. malayi by comparing developmental stages in the mosquito relative to those in the mammalian host, providing insight into gene expression changes underpinning the mosquito-borne parasitic lifestyle of this heteroxenous parasite. Overall design: Time-course mRNA profiles of filarial parasite Brugia malayi and host mosqutio Aedes aegypti were generated by deep sequencing using Illumina GAIIx.

从本质而言，寄生虫生物学若不与宿主生物学相结合便无法得到完整理解，而宿主的应答反应若不考虑寄生虫的活动也无法得到充分阐释。然而，受限于实验技术瓶颈，寄生虫-宿主互作系统的分子研究长期以来多为单一偏向性的调查，仅聚焦于二者其一。本研究针对丝虫寄生虫与宿主蚊子开展联合双转录组测序（dual RNA-seq）时间序列分析，以期更深入解析从感染建立至感染性幼虫逸出的全过程中，寄生虫在宿主组织内发育及与之互作的核心过程。本研究以马来布鲁线虫（Brugia malayi）-埃及伊蚊（Aedes aegypti）为研究系统，揭示了寄生虫的基因转录动态特征：其呈现出一套高度有序的发育程序，包含一系列周期性与状态转换型的时间表达模式。同时，我们将寄生虫转录组数据与宿主转录组的同步动态变化进行关联分析。通过对比未感染组织与不同宿主品系的样本，我们明确了寄生虫发育对宿主基因转录的调控作用，以及宿主微环境对寄生虫基因转录的影响。此外，我们通过对比该寄生虫在蚊体内与哺乳动物宿主体内的发育阶段转录组，对马来布鲁线虫的生命周期转录组进行批判性评估，为解析这种异宿主寄生（heteroxenous parasite）虫种以蚊媒方式传播的寄生生活方式背后的基因表达调控机制提供了新视角。实验设计概述：本研究通过Illumina GAIIx平台开展深度测序，获取了丝虫寄生虫马来布鲁线虫（Brugia malayi）与宿主埃及伊蚊（Aedes aegypti）的时间序列mRNA表达谱。