Abstract:
Some parasitic diseases, such as malaria, require two hosts to complete their lifecycle: a human and an insect vector. Although most malaria research has focused on parasite development in the human host, the life cycle within the vector is critical for the propagation of the disease. The mosquito stage of the Plasmodium lifecycle represents a major demographic bottleneck, crucial for transmission blocking strategies. Furthermore, it is in the vector, where sexual recombination occurs generating \"de novo\" genetic diversity, which can favor the spread of drug resistance and hinder effective vaccine development. However, understanding of vector-parasite interactions is hampered by the lack of experimental systems that mimic the natural environment while allowing to control and standardize the complexity of the interactions. The breakthrough in stem cell technologies has provided new insights into human-pathogen interactions, but these advances have not been translated into insect models. Here, we review in vivo and in vitro systems that have been used so far to study malaria in the mosquito. We also highlight the relevance of single-cell technologies to progress understanding of these interactions with higher resolution and depth. Finally, we emphasize the necessity to develop robust and accessible ex vivo systems (tissues and organs) to enable investigation of the molecular mechanisms of parasite-vector interactions providing new targets for malaria control.
摘要:
一些寄生虫病,比如疟疾,需要两个宿主来完成它们的生命周期:人类和昆虫媒介。尽管大多数疟疾研究都集中在人类宿主中的寄生虫发育,媒介内的生命周期对疾病的传播至关重要。疟原虫生命周期的蚊子阶段是一个主要的人口瓶颈,对于传输阻断策略至关重要。此外,它在向量中,性重组发生在产生“从头”遗传多样性的地方,这可能有利于耐药性的传播并阻碍有效疫苗的开发。然而,由于缺乏模拟自然环境的实验系统,同时允许控制和标准化相互作用的复杂性,因此阻碍了对媒介-寄生虫相互作用的理解。干细胞技术的突破为人类与病原体的相互作用提供了新的见解,但是这些进步还没有转化为昆虫模型。这里,我们回顾了迄今为止用于研究蚊子中疟疾的体内和体外系统。我们还强调了单细胞技术的相关性,以更高的分辨率和深度促进对这些相互作用的理解。最后,我们强调必须开发健壮和可访问的离体系统(组织和器官),以便能够研究寄生虫-载体相互作用的分子机制,为疟疾控制提供新的靶标。