MOLECULAR STUDY OF INSECT VECTOR ANTIHEMOSTATIC FACTORS

描述(改编自申请人的摘要)：为了能够以血液为食，蚊子媒介通过一些唾液因子改变脊椎动物宿主对伤害的反应，这些因素抑制止血和炎症，并最终改变免疫反应。这些修饰可能会增强寄生虫和病原体入侵人类宿主的能力。PI提出了四个具体目标：(1)表征埃及伊蚊和斯氏按蚊唾液中调节脊椎动物免疫反应的分子(在BALB/c小鼠模型中)。这些分子将被提纯、克隆、测序并以重组蛋白的形式表达。(2)明确蚊虫唾液和唾液蛋白对B细胞、T细胞、巨噬细胞和朗格汉斯细胞反应的影响。蚊子唾液在蚊子进食部位产生局部免疫抑制区的假设将得到验证。将检测载体唾液对Th1(细胞毒)Th2(体液)免疫反应发展的影响。(3)明确蚊虫唾液和个别唾液蛋白的全身或全身免疫调节作用。(4)测试病原体和寄生虫以一种可能增强媒介效能的方式改变媒介的唾液的假设。这些研究最终旨在了解媒介饲养的免疫学后果。对媒介传播的病原体和寄生虫传播到的免疫环境的了解可能会导致干扰传播的新策略。

DESCRIPTION (Adapted from the Applicant's Abstract): To be able to feed on blood, a mosquito vector modifies the response of the vertebrate host to injury, through a number of salivary factors that inhibit hemostasis and inflammation, and ultimately modify immune responses. These modifications are likely to enhance the ability of parasites and pathogens to invade the human host. The PI proposes four specific aims: (1) Characterize the molecules in Aedes aegypti and Anopheles stephensi saliva that modulate vertebrate immune responses (in a BALB/c mouse model). These molecules will be purified, cloned, sequenced and expressed as recombinant proteins. (2) Define the effects of mosquito saliva and salivary proteins on responses of B- and T- cells, macrophages, and Langerhans cells. The hypothesis that mosquito saliva creates a locally immunocompromized zone at the site of mosquito feeding will be tested. The influence of vector saliva on the development of Th1 (cytotoxic) Th2 (humoral) immune responses will be examined.. (3) Define the systemic or whole body immunomodulatory effects of mosquito saliva and individual salivary proteins. (4) Test the hypothesis that pathogens and parasites modify the saliva of vectors in a manner likely to enhance their vectorial efficacy. These studies are ultimately directed towards an understanding of the immunological consequences of vector feeding. An understanding of the immune environment into which vector-born pathogens and parasites are transmitted may lead to novel strategies for disrupting the transmission.