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

蚊子SAMSP1和SAMSP2对小鼠疟原虫感染初期的影响

• 批准号: 10589090
• 负责人: George Dimopoulos
• 金额: $ 80.78万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-14 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589090
• 关键词: Active Immunization; Affect; Anopheles Genus; Anopheles gambiae; Bite; Blocking Antibodies; Blood Vessels; Cells; Cellular Immunity; Clustered Regularly Interspaced Short Palindromic Repeats; Culicidae; Data; Deposition; Dermis; Development; Gene Expression; Gene Silencing; Gene Transfer Techniques; Human; Image; Immune; Immune response; Immunity; Immunization; In Vitro; Infection; Invaded; Lead; Malaria; Malaria Vaccines; Measures; Movement; Mus; Passive Immunization; Phase; Plasmodium; Proteins; RNA Interference; Role; Saliva; Serum; Site; Skin; Speed; Sporozoites; T-Lymphocyte; Testing; cell motility; combat; immunoregulation; in vitro Assay; in vivo; intradermal injection; intravital imaging; loss of function; migration; mosquito-borne; overexpression; pathogen; transcriptome sequencing; transcriptomics; transmission process; two photon microscopy; two-photon; vector

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.

摘要 这一建议将阐明蚊子唾液中的两种特异性蛋白质如何影响早期阶段的 小鼠疟原虫感染。我们的小组以前开发了一种通用筛选来识别 冈比亚按蚊唾液与子孢子在移出蚊子和沉积过程中的结合 进入哺乳动物宿主的皮肤（Schleicher 格雷厄姆 [10]杨J，弗劳德松M，伦比兹A，克拉夫特S，汉密尔顿M， [10]李勇，克雷斯韦尔，辛尼斯，丁茂波，李明. Nat Commun. 2018 25;9（1）：2908）。鉴定了几种蛋白质，包括子孢子相关的蚊子唾液蛋白 （SAMSP）1和SAMSP 2。我们的初步数据表明，SAMSP 1在促进疟原虫 感染小鼠，且SAMSP 2具有免疫调节活性。本提案现在将审查 SAMSP 1和SAMPS 2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 感染真皮的体内双光子显微镜检查，以及评估运动和免疫的体外测定。 调节，将描绘SAMSP 1和SAMSP 2对子孢子活性的影响。了解 SAMSP 1和SAMSP 2在疟原虫感染中的重要性有望导致新的防治策略 疟疾