Olfactory mechanisms underlying behavioural manipulation of mosquitoes by malaria parasites

寄生虫有能力操纵参与其传播的昆虫的行为，以增强自身的生殖适合性。例如，感染疟疾的蚊子比未感染的蚊子摄取更多的血餐，并将摄取多次血餐。在申请者最近进行的一项初步研究中，我们证明了非洲最重要的疟疾蚊种之一冈比亚按蚊感染了恶性疟原虫的雌性蚊子比未感染的蚊子更容易被人类气味吸引。恶性疟原虫是导致人类疟疾的最重要寄生虫之一。这是一种变化的第一次演示。冈比亚亚种对感染疟疾寄生虫恶性疟原虫引起的人类气味的反应行为。这一行为具有根本重要性，因为它将提高疾病传播的效率。我们建议探索这种反应的机制。这项研究的假设是恶性疟原虫操纵寻找宿主的嗅觉系统。冈比亚雌性蚊子使它们对宿主刺激更敏感，这导致受感染的蚊子更容易被人类宿主吸引。我们建议在初步研究的基础上，使用风洞生物测定来量化蚊子的行为反应。冈比亚亚种将感染人类疟疾寄生虫恶性疟原虫的雌性蚊子与未感染的雌性蚊子进行比较，并确定这种反应是否取决于蚊子体内寄生虫的生命周期阶段。我们将在伦敦卫生和热带医学院专门设计的安全实验室内使用嗅觉仪进行研究，这些研究旨在测量昆虫对人类气味的行为反应。为了确定疟原虫感染对嗅觉系统(即蚊子的嗅觉)的影响，我们将使用一种电生理学技术，使我们能够记录蚊子的触角对组成人体气味的复杂混合物中个别化合物的反应。这一技术加上其他最先进的分析化学技术，将使我们能够识别蚊子可以检测到的挥发性化合物，并确定受感染的蚊子对人类向未感染蚊子排放的气味挥发物的反应是否不同。我们的研究结果将提供信息，可用于阐明疟疾是如何通过蚊子在人类之间传播的。冈比亚亚种女性。重要的是，可以确定新的有吸引力的化合物，这些化合物可以用于开发改进的蚊子诱捕器，用于监测或诱捕计划，甚至可能专门针对感染恶性疟原虫的蚊子。冈比亚亚种女性。这项研究将是一个基本的例子，说明寄生虫如何能够操纵它们的宿主来增加自己的生殖适合度。

Parasites have the ability to manipulate the behaviour of the insects that are involved in their transmission to enhance their own reproductive fitness. For example, malaria-infected mosquitoes take larger blood meals than uninfected ones, and will take multiple blood meals. In a pilot study, conducted recently by the applicants, we demonstrated that females of one of the most important African malaria mosquito species Anopheles gambiae sensu stricto infected with Plasmodium falciparum, one of the most important parasites that causes malaria in human beings, were significantly more attracted to human odours than uninfected mosquitoes. This was the first demonstration of a change in An. gambiae s.s. behaviour in response to human odours caused by infection with the malaria parasite P. falciparum. This behaviour is of fundamental importance since it will enhance the efficiency of disease transmission. We propose to explore the mechanisms for this response. The hypothesis of the proposed study is that P. falciparum parasites manipulate the olfactory system of host-seeking An. gambiae female mosquitoes making them more sensitive to host stimuli and this causes infected mosquitoes to be more attracted to human hosts.We propose to build on our preliminary study to quantify, using a windtunnel bioassay, the behavioural responses of An. gambiae s.s. female infected with human malaria parasites, P. falciparum, compared to uninfected females and determine whether the response depends on the lifecycle stage of the parasites within the mosquito. We will use olfactometer studies, which are designed to measure the behavioural response of the insects to human odours, within specially designed secure laboratories at the London School of Hygiene and Tropical Medicine. To determine the effect of a Plasmodium infection on the olfactory system (i.e. the mosquito's sense of smell), we will use an electrophysiology technique which allows us to record the response of the mosquito's antenna to individual compounds within the complex mixture that makes up human body odour. This, along with other state-of-the-art analytical chemistry techniques, will allow us to identify the volatile compounds that the mosquito can detect and to determine whether infected mosquitoes respond differently to the odorous volatiles emitted by humans to uninfected mosquitoes.The results of our study will provide information that could be used to illuminate how malaria is transmitted between human beings by An. gambiae s.s. females. Importantly, new attractive compounds could be identified which could be used to develop improved mosquito traps for surveillance or trapping programmes that may even specifically target P. falciparum-infected An. gambiae s.s. females. This study will be a fundamental example of how parasites are able to manipulate their host to increase their own reproductive fitness.