Immune interactions between insects and parasites

昆虫传播寄生虫，对人类和动物造成重大疾病。疟疾、淋巴丝虫病等毁灭性疾病每年夺去200万至300万人的生命，登革热和西尼罗河病毒等病毒导致数百万人患病或死亡。我们的研究涉及昆虫媒介和它们传播的病原体之间的分子相互作用。大多数昆虫利用免疫系统的成分杀死进入它们体内的寄生虫。这种反应在很大程度上是基于产生与细菌、真菌、病毒和寄生虫结合并杀死它们的小肽。首先，寄生虫必须被识别为“非自我”，从而启动免疫因子的表达。该提案将研究长角锥虫（Rhodnius prolixus）的免疫反应。长角锥虫是克氏锥虫的一种病媒，在北美、中美洲和南美洲感染了1800万人。这种寄生虫的独特之处在于，它改变了自己的生命周期，以避免进入免疫反应最强的昆虫区域。我们将描述参与非自我识别、激活、调节和表达免疫肽的分子，以应对细菌、真菌和寄生虫的感染，并将识别对这些生物致命的新肽。我们还将通过沉默这些分子的表达来确定它们的作用，看看寄生虫的数量是否会改变，或者昆虫本身是否会死亡。最终，我们想确定我们是否可以阻止寄生虫的发展，从而阻止传播，或者我们是否可以识别和评估这些分子作为治疗细菌和寄生虫感染的潜在药物。

Insects transmit parasites that cause significant disease to humans and animals. Devastating diseases such as malaria, lymphatic filariasis kill 2-3 million people per year and viruses such as Dengue and West Nile virus cause illness or death in millions more. Our research addresses the molecular interactions between insect vectors and the pathogens they transmit. Most insects kill parasites that enter their bodies using components of their immune system. This response is based in a large part on the production of small peptides that bind to, and kill, bacteria, fungi, viruses and parasites. The parasite first must be recognized as "non-self" which initiates the expression of immune factors. This proposal will look at the immune response of Rhodnius prolixus, a vector of Trypanosoma cruzi that infects 18 million people in North, Central and South America. This parasite is unique in that it has modified its life-cycle to avoid entering regions of the insect where immune responses are strongest. We will characterize molecules involved in non-self recognition, activation, regulation and expression of immune peptides in this vector in response to infections with bacteria fungi, and parasites, and will identify novel peptides that are lethal to these organisms. We will also determine the role of these molecules by silencing their expression to see if parasite numbers change or if the insects themselves die. Ultimately we would like to determine if we can stop parasite development, and therefore stop transmission, or if we can identify and evaluate these molecules as potential drugs to treat people with bacterial and parasitic infections.