艾德斯在人皮肤上的白photictus。来源：CDC

每年，蚊子传播的病毒，例如登革热，基孔肯雅亚和最近，寨卡病毒引起了数亿个感染。这些爆发的不可预测的本质，再加上这些病毒的巨大遗传多样性，使得为当前和未来威胁准备疫苗或抗病毒药物的挑战。目前，疫苗很少，没有可用于治疗的抗病毒药。对许多此类病毒制定共同的策略不是很棒吗？

这些病毒大多数共同的一件事是，它们是由有限数量的艾德斯蚊子物种，特别是Ae。白化病andAe。aegypti。These mosquitoes are rapidly increasing their territories due to气候变化和全球化，，，，facilitating the large outbreaks of viruses such as chikungunya and Zika we’ve seen in the past decade.

几个研究小组观察到蚊子的存在，甚至只是唾液的存在，增加病毒传播和发病率。

My colleagues and I at the University of Leeds have just我们调查的已发表结果进入这种有趣的观察的基础机制。

Our model system

为了调查蚊子叮咬的影响，我们允许Ae。aegypti咬一小块鼠标皮肤。然后将咬伤或静止的皮肤注射，并注入少量的蚊子衍生的semliki森林病毒。这样，我们在高度可重复的模型中模仿自然感染。

免疫系统如何使病毒受益

We found that the rapid, local immune response to the mosquito bites is actually beneficial for the virus. An oedematous bump, well known to occur after a mosquito bite, retains virus in the skin. Here, a strong innate immune response is orchestrated to fix the damage caused by the mosquito bite. However, unwittingly this immune response also results in giving the virus an early and powerful advantage.

蚊虫叮咬中病毒感染的增强是由于免疫细胞的募集。第一轮招募的细胞是neutrophils。这些高度移动的细胞很早就开始进行组织修复并抗击感染。中性粒细胞似乎并没有被感染，而是导致保留皮肤病毒的水肿。

募集第二波免疫细胞，单核细胞andmacrophages然后发生。巨噬细胞吞噬了可能发起合适的免疫反应的任何可能危险的东西。但是，这些巨噬细胞被感染并产生大量病毒，这有助于病毒在体内的传播，包括大脑，它们在我们的小鼠模型中引起疾病​​。

如何防止这个

当我们用抗体耗尽嗜中性粒细胞，或通过使用与固定巨噬细胞的基因敲除小鼠来防止巨噬细胞迁移到咬合部位时，我们阻止了咬合咬合。

我们调查了叮咬是否是蚊子唾液的直接作用，它通过将其效力与各种炎症药物进行比较，这些炎症药通过完全不同的机制募集了相似的细胞类型。这包括细菌脂蛋白（PAM3CSK4）和疫苗辅助校友的合成模仿。有趣的是，蚊子唾液以类似于这些测试化合物的方式增强了病毒感染。

我们认为这种早期和局部免疫反应可能为我们提供了预防疾病的有用目标。因此，我们通过靶向该局部免疫反应的一个成分之一，即有效的促炎分子，测试了这一想法。IL-1ß，，，，by pre-treating the mice with a blocker that prevents activation of IL-1ß.

We were able to reduce the bite enhancement effect and improve disease outcome by inhibiting the inflammatory response that occurs at the bite site.

A potential future clinical application of these findings

Our current research focuses on improving our understanding of early events in the bitten skin and what aspects of mosquito bites impact local inflammation. In addition, we are testing ways to modulate this early immune response to improve disease outcome.

因为这些病毒主要是通过刺激性传播的Ae。白化病andAe。aegypti，，，，it is likely you would notice that you have been bitten within a few hours. This could provide a time window that is long enough to modulate the early immune response, for instance by applying a cream. Although it is best not to get bitten at all, we hope that applying anti-inflammatory cream onto mosquito bites could prevent bite-enhancement and thus reduce disease caused by many different viruses.