The mechanisms underlying the production of natural mosquito repellents by human beings

有些人比其他人更容易被蚊子叮咬。从进化的角度来看，这是非常重要的，因为那些被咬得更少的人更不可能死于致命的蚊子传播疾病，比如疟疾。因此，对疟疾蚊子的吸引力较低可能是一种选择优势。这是由于人类的自然选择，还是因为蚊子只是为了避开不合适的宿主，目前还不清楚，但我们之前的研究表明，人类对蚊子的不同吸引力是由于很少被叮咬的个体自然产生的关键驱蚊化学物质。从本质上讲，这可以被认为是与免疫系统相关的第一道防线。在最近的一项初步研究中，我们表明，对欧洲人来说，你对蚊子的吸引力是由你的基因控制的。我们打算扩大这一研究范围，在传统上受到疟疾强烈选择压力的非洲土著人口中开展类似的研究。在这里，我们期望找到正在选择中的新驱避分子的基因。我们从对欧洲人的研究中发现，天然的驱蚊化学物质在涂抹在皮肤上时是有效的，但我们仍然不知道身体是如何产生这些化学物质的，以及哪些基因控制了这一过程。初步研究表明，一些驱蚊剂可以由皮肤细胞产生，可能存在候选基因作为潜在靶点。在这项研究中，我们的目标是使用化学生态学和分子遗传学技术来比较同卵和异卵双胞胎，以确定化学物质是如何产生的，以及哪些基因参与了生产和调节。这将使人们了解人体如何提供对蚊子天然抗性的重要组成部分，并提供一种新的潜在治疗方法，刺激易感人群产生这些驱蚊化学物质。这可以让我们开发出一种更持久的应用，并最终以药丸的形式口服治疗，从而提高天然驱蚊剂的产量，以防止蚊虫叮咬，最大限度地减少对反复涂抹皮肤的挥发性驱蚊剂的需求。这项研究有可能找到可以系统生产的新型驱蚊剂，并阐明最不为人所知的先天免疫机制之一：我们如何利用化学战来躲避载体。

Some human beings are bitten more than others by mosquitoes. From an evolutionary perspective this is fundamentally important since those that get bitten less often are less likely to die from lethal mosquito-borne diseases like malaria. Thus there is likely to be a selective advantage for being less attractive to malaria mosquitoes. Whether or not this is due to natural selection in humans, or because mosquitoes are simply avoiding unsuitable hosts is unknown, but our previous studies show that human differential attractiveness to mosquitoes is due to the natural production of key repellent chemicals given off by individuals who rarely get bitten. Essentially this could be thought of as the first line of defence related to the immune system. In a recent pilot study we showed that for Europeans how attractive you are to mosquitoes is controlled by your genes. We intend to extend this line of research and carry out a similar study amongst an indigenous African population that has traditionally been under intense selective pressure from malaria. Here we would anticipate finding genes for new repellent molecules that are under selection. The natural repellent chemicals that we have identified from our study of Europeans are effective repellents when applied to the skin, but what remains unknown is how the body produces these chemicals and which genes control this process. Preliminary studies show that some of the repellents can be produced by skin cells and there are likely candidate genes as potential targets. In this study we aim to compare identical and non-identical twins using chemical ecology and molecular genetic techniques to identify how the chemicals are produced and which genes are involved in production and regulation. This will give an understanding of how the body provides an important component of natural resistance to mosquitoes and provide a new potential treatment which stimulates production of these repellent chemicals in susceptible human beings. This could allow us to develop a more persistent application and eventually an oral treatment in the form of a pill which enhances the production of natural repellents to protect against mosquito bites, minimising the need for repeated skin-applied volatile repellents. This research has the potential to find new mosquito repellents that could be produced systemically, and elucidate one of the least understood innate immunity mechanisms: how we use chemical warfare to hide from vectors.