Mosquito SAMSP1 and SAMSP2 influence the initial stage of Plasmodium infection of mice

摘要 这项建议将阐明蚊子唾液中的两种特定蛋白质如何影响早期的蚊子 小鼠的疟原虫感染。我们的团队之前开发了一种通用筛查方法来识别 冈比亚按蚊在移出蚊子和沉积过程中与子孢子相关的唾液 进入哺乳动物宿主(Schleicher)的皮肤 格雷厄姆 杨静，M，雷姆比兹，S，汉密尔顿 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容2018年 25；9(1)：2908)。确定了几种蛋白质，包括与子孢子相关的蚊子唾液蛋白 (SAMSP)1和SAMSP2。我们的初步数据表明，SAMSP1在促进疟原虫生长方面发挥了作用 SAMSP2具有免疫调节活性。这项提案现在将审查 SAMSP1和SAMPS2在影响小鼠疟原虫感染初期的重要性。基因 沉默和抗体阻断研究将评估这些蛋白质在小鼠早期阶段的作用 感染。真皮的活体双光子显微镜，以及评估运动和免疫的体外试验 将描述SAMSP1和SAMSP2对子孢子活性的影响。了解 SAMSP1和SAMSP2在疟原虫感染中的重要性有望带来新的抗击策略 疟疾。

ABSTRACT This proposal will elucidate how two specific proteins in mosquito saliva influence the early stage of Plasmodium infection in mice. Our group previously developed a general screen to identify proteins in Anopheles gambiae saliva that associate with sporozoites during movement out the mosquito and deposition into the skin of a mammalian host (Schleicher Graham TR, Yang J, Freudzon M, Rembisz A, Craft S, Hamilton M, M, Mlambo G, Tripathi AK, Li Y, Cresswell P, Sinnis P, Dimopoulos G, Fikrig E. Nat Commun. 2018 25;9(1):2908). Several proteins were identified, including sporozoite-associated mosquito saliva protein (SAMSP) 1 and SAMSP2. Our preliminary data shows that SAMSP1 plays a role in facilitating Plasmodium infection in mice and that SAMSP2 has immunomodulatory activity. This proposal will now examine the importance of SAMSP1 and SAMPS2 in influencing the initial stage of Plasmodium infection in mice. Gene silencing and antibody blocking studies will assess the role of these proteins in the early stages of murine infection. In vivo two-photon microscopy of the dermis, and in vitro assays to assess movement and immune modulation, will delineate the effects of SAMSP1 and SAMSP2 on sporozoite activity. Understanding the importance of SAMSP1 and SAMSP2 in Plasmodium infection will hopefully lead to new strategies to combat malaria.