Tick feeding regulation by orthologous tick saliva serine protease inhibitors

直系同源蜱唾液丝氨酸蛋白酶抑制剂对蜱摄食的调节

• 批准号: 8087210
• 负责人: ALBERT MULENGA
• 金额: $ 24.87万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-16 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8087210
• 关键词: Adult; Amblyomma; Amino Acids; Antibodies; Antibody Formation; Anticoagulants; Antigen Targeting; Antigens; Arthropod Vectors; Babesiosis; Basophils; Biological Assay; Black-legged Tick; Blood; Blood coagulation; Bovine Anaplasmosis; Cathepsin G; Cells; Chymase; Complement Activation; Containment; Data; Deer; Development; Ehrlichia chaffeensis; Ehrlichiosis; Enzyme-Linked Immunosorbent Assay; Exanthema; Future; Gene Bank; Goals; Harvest; Host Defense; Human; Immunity; Immunization; Immunosuppressive Agents; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Injection of therapeutic agent; Leukocyte Elastase; Lyme Disease; Mediating; Methods; Natural Immunity; Nature; Nymph; Orthologous Gene; Pathway interactions; Physiology; Protein Sequence Analysis; Proteinase 3; Proteins; Protocols documentation; Proxy; Reaction; Recombinants; Regulation; Research; Ricinus plant; Role; Saliva; Salivary Glands; Secondary Immunization; Serine Protease; Serine Proteinase Inhibitors; Site; Tail; Tick Control; Tick Infestations; Tick-Borne Diseases; Ticks; Tryptase; United States; Vaccines; Validation; Vector-transmitted infectious disease; Western Blotting; acaricide; base; defense response; feeding; mast cell; new technology; prevent; programs; success; synthetic peptide

DESCRIPTION (provided by applicant): In the United States human vector borne diseases are primarily tick borne. The goals of this research are identification, characterization and validation of Amblyomma americanum and Ixodes scapularis tick saliva serine protease inhibitors (serpins) as vaccine target antigens for immunization of white tailed deer against tick infestation. To complete feeding, ticks must overcome host defense reactions, blood coagulation, complement activation and inflammation, all of which are serine protease mediated pathways that are tightly controlled by serpins. Our lab and others have proposed that during feeding, ticks express and inject serpins into the host to regulate evasion of host defense response to tick feeding activity. In an ongoing NIHR03 project in its final year we have screened 10 A. americanum (Aam) tick salivary gland (SG) serpin, and validated that 2 of the serpins (S), AamS6 and AamS8 are secreted into tick saliva, which is proxy for their injection into the host during tick feeding. We have extended these studies and identified 14 blood meal responsive I. scapularis tick SG serpins. In this proposal we will utilize protocols developed in the NIHR03 project to validate secretion of the 14 I. scapularis SG serpins into tick saliva. We have observed that the two A. americanum tick saliva serpins as well as the I. ricinus tick saliva serpin are highly conserved in ticks. Thus, we hypothesize that ticks utilize orthologous tick saliva serpins to regulate tick feeding and that immunologically blocking tick saliva serpin functions will prevent feeding success of multiple tick species. The importance of white tailed deer (Odocoileus virginianus) in the emergence of major human tick borne diseases (TBD) in the United States, Lyme disease, human anaplasmosis, babesiosis and ehrlichiosis and the southern tick-associated rash illness (STARI) has been recognized. Thus data in this proposal will be directly relevant towards efforts to develop novel technologies to prevent human TBD. There are 3 specific aims in this application. The first is to validate secretion of 16 blood meal responsive I. scapularis tick salivary gland serpins into tick saliva. The second is to characterize role(s) of A. americanum and I. scapularis native tick saliva serpins in tick feeding regulation. To validate tick immunity and anamnestic antibody response to tick infestation of white tailed deer immunized with recombinant tick saliva serpin antigens. PUBLIC HEALTH RELEVANCE: In the United States ticks transmit more vector borne disease agents than any other vector arthropod. Limitations associated with current acaricide based tick control strategies that threaten the future sustainability of containment programs for tick borne illnesses, have necessitated the need for development of alternative tick control strategies. Identification of important tick proteins that regulate tick physiology and facilitate tick feeding is important before alternative tick control methods can be developed.

描述（由申请人提供）：在美国，人类向量传播疾病主要是tick虫。这项研究的目标是鉴定，表征和验证Amblyomma Americanum和Ixodes capularis tick tick唾液丝氨酸丝氨酸蛋白酶抑制剂（SERPINS）作为疫苗靶抗原，用于免疫白色尾鹿抗tick虫。为了完成喂养，壁虱必须克服宿主的防御反应，血液凝结，补体激活和炎症，所有这些都是丝氨酸蛋白酶介导的途径，这些途径由Serpins紧紧控制。我们的实验室和其他人提出，在喂食期间，tick滴s将丝氨酸表达并注入宿主中，以调节逃避宿主防御反应的滴答喂食活动。在最后一年的一个正在进行的NIHR03项目中，我们对10 A. Americanum（AAM）Tick唾液腺（SG）Serpin进行了筛选，并验证了Serpins（S），AAMS6和AAMS8中的2个被分泌到Tick唾液中，这是在Tick Feeding期间注入主机的代理。我们已经扩展了这些研究，并确定了14次血液粉反应。在此提案中，我们将利用NIHR03项目中开发的协议来验证14 I. scapularis sg serpins的分泌成tick唾液。我们已经观察到，两个Americanum Tick唾液丝氨酸以及I. Ricinus Tick Saliva Serpin在tick虫中高度保守。因此，我们假设使用直系同源滴答唾液丝氨酸来调节tick喂食，并且免疫学上阻止tick唾液serpin功能将阻止多个tick虫的喂养成功。白尾鹿（弗吉尼亚尼亚斯）在美国的主要人虫疾病（TBD）中的出现，莱姆病，人类疾病，人类肿瘤，巴布西病和ehrllichiisois和南方tick虫相关的皮疹疾病（STARI）的重要性已得到认可。因此，该提案中的数据将与开发新技术以防止人类TBD的努力直接相关。该应用程序中有3个具体目标。首先是验证16个血液粉反应的分泌。第二个是表征A. Americanum和I. capularis tick唾液丝氨酸在tick喂食调节中的角色。为了验证tick免疫力和对用重组tick唾液serpin抗原免疫的白色尾鹿的tick虫侵扰的滴答抗体反应。 公共卫生相关性： 在美国，tick传输的媒介代理比任何其他载体节肢动物都要多。与当前基于Acaricide的壁虱控制策略相关的限制，这些策略威胁着tick虫疾病的遏制计划的未来可持续性，因此需要开发替代性tick控制策略。在开发替代tick控制方法之前，鉴定调节壁虱生理和促进滴答的重要tick蛋白很重要。