MOLECULAR STUDY OF INSECT VECTOR ANTIHEMOSTATIC FACTORS

为了能够以血液为食，蚊子载体通过许多抑制止血和炎症的唾液因子来改变脊椎动物宿主对损伤的反应，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应答的分子（在BALB/c小鼠模型中）。这些分子将被纯化、克隆、测序并表达为重组蛋白。(2)确定蚊子唾液和唾液蛋白对B细胞和T细胞、巨噬细胞和朗格汉斯细胞反应的影响。将测试蚊子唾液在蚊子进食部位产生局部免疫受损区的假设。将检查载体唾液对Th 1（细胞毒性）Th 2（体液）免疫应答发展的影响。(3)定义蚊子唾液和个别唾液蛋白的系统或全身免疫调节作用。(4)检验病原体和寄生虫以可能增强其媒介效力的方式修改媒介唾液的假设。这些研究最终旨在了解病媒喂养的免疫后果。了解媒介传播的病原体和寄生虫传播的免疫环境可能会导致破坏传播的新策略。

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.