Tick Saliva and Pathogen Transmission

蜱唾液和病原体传播

• 批准号: 9884713
• 负责人: Joao Pedra
• 金额: $ 55.54万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-09 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9884713
• 关键词: Address; Affect; Anaplasma phagocytophilum; Annexins; Anti-Inflammatory Agents; Antigens; Area; Arthropod Vectors; Arthropods; Baltimore; Binding; Biological Markers; Biology; Black-legged Tick; Blood; Borrelia burgdorferi; CASP1 gene; Cells; Communicable Diseases; Communities; Data; Defect; Dendritic Cells; Enzyme Activation; Enzymes; Exhibits; Family; Growth; Homeostasis; Hour; Immune; Immune Evasion; Immune Targeting; Immune signaling; Immunity; Immunologics; Impairment; Infection; Inflammasome; Inflammation; Inflammatory; Interleukin-1 beta; Interleukin-18; Ixodes; Laboratories; Life; Location; Lymphatic; Lymphatic System; Maryland; Medicine; Mus; New York City; Oxidative Stress; Pathway interactions; Play; Post-Translational Protein Processing; Principal Investigator; Process; Proteins; Public Health; Publishing; RNA Interference; Reporting; Research; Research Personnel; Rickettsia; Role; Salivary; Salivary Proteins; Scaffolding Protein; Skin; System; Testing; Tick-Borne Diseases; Ticks; Training; Universities; Vaccines; authority; base; college; cytokine; density; exosome; extracellular vesicles; feeding; human pathogen; immunoregulation; insight; intercellular communication; medical schools; microbial; mid-career faculty; novel; pathogen; professor; response; success; tick feeding; tick saliva; transmission process; vector

Summary/Abstract: Ticks are hematophagous ectoparasites with worldwide public health and veterinary importance. The success of their life strategy can be attributed, in part, to anti-inflammatory salivary proteins that inhibit host immunity and facilitate pathogen transmission. As an example, we recently discovered a novel mechanism of immune evasion by which the Ixodes scapularis salivary protein Sialostatin L2 inhibits activation of the NLRC4 inflammasome. The NLRC4 inflammasome is a protein scaffold that regulates maturation of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 through the enzyme caspase-1. We demonstrated that Sialostatin L2 binds to the mammalian host protein Annexin A2. Upon infection with the rickettsial pathogen Anaplasma phagocytophilum, Sialostatin L2 impairs assembly of the NLRC4 inflammasome. How tick effector molecules, such as Sialostatin L2, are released during blood-feeding continues to be unknown. In what manner pathogens, such as A. phagocytophilum, influence the delivery of tick molecules to the mammalian host remain elusive. Whether the lymphatic system, a network of circulatory vessels, provides a rapid mechanism of dissemination for immunological information during tick blood-feeding remains undetermined. Exosomes are small extracellular vesicles that function in intercellular communication, facilitating host immune modulation. For this R01 application, we show that I. scapularis exosomes interact with host immune cells and transport anti-inflammatory tick salivary proteins. We report that A. phagocytophilum alters the oxidative state of molecules within exosomes. Finally, we demonstrate that the lymphatic system acts as a conduit where the release of tick proteins may affect inflammation. Accordingly, our central hypothesis states that the lymphatic system plays a critical role in modulating inflammation during tick feeding; and that exosomes facilitate intercommunication between I. scapularis and the mammalian host. Aim#1 of this proposal will identify anti- inflammatory molecules within tick exosomes. Aim#2 will define oxidative post-translational modifications within tick exosomes. Aim#3 will evaluate the role of the lymphatic system during tick feeding. Altogether, this research will determine how tick-derived exosomes transport salivary proteins; investigate the underlying mechanisms by which the rickettsial pathogen A. phagocytophilum affects exosomes; and reveal whether the lymphatic system carries tick-derived molecules. As ticks and other arthropods transmit many human pathogens during feeding, solving this intriguing scientific question will provide critical insights to the vector biology community.

摘要/摘要：蜱是一种世界性的食血性体外寄生虫