ROLE OF DENDRITIC CELLS IN REGULATING VACCINE- INDUCED IMMUNITY AGAINST Q FEVER

摘要 贝氏柯克斯体是一种专性细胞内革兰氏阴性细菌，可引起急性和慢性Q热， 人类迫切需要创造一种安全有效的疫苗来预防人类Q热。 然而，疫苗诱导的抗C.贝氏自然感染仍不清楚。 该项目的长期目标是开发一种安全有效的Q热疫苗。的目标 这一应用是实现这一目标的关键一步，目的是了解树突状细胞（DC）在 调节疫苗诱导的抗Q热免疫，并确定哪种类型的T细胞反应更关键 疫苗诱导的保护性免疫为了实现这一目标，提出了两个具体目标来测试 中心假设C.贝氏I期疫苗（PIV）和II期疫苗（PIIV）差异激活 DC，从而促进不同的T细胞应答，是它们赋予免疫应答能力差异的原因。 保护目的1将确定DC在调节疫苗诱导的抗Q热免疫中的作用， 检查i）PIV和PIIV是否差异性地激活DC，从而促进不同的T细胞分化模式 在小鼠模型中;和ii）DC是否在疫苗诱导的针对C.贝氏气溶胶感染 in vivo.目的2探讨CD 4 + T细胞亚群在PIV诱导的抗C. 通过使用小鼠模型研究贝氏气溶胶感染，i）PIV和PIV诱导的T细胞应答 负责其赋予保护能力的差异;和ii）哪种CD 4+亚群T细胞应答 对PIV诱导的保护作用更为关键。作为本研究的成果，它将为 了解DC在调节T细胞介导的免疫中的作用，并确定T细胞 疫苗诱导的抗C.贝氏体感染预计这将使 对健康的重大积极影响，因为它将提供关键信息，为发展一个安全的 和有效的Q热疫苗

Abstract Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes acute and chronic Q fever in humans. There is an urgent need to create a safe and effective vaccine for prevention of human Q fever. However, the mechanisms of vaccine-induced immunity against C. burnetii natural infection remain unclear. The long-term goal of this project is to develop a safe and effective vaccine against Q fever. The objective of this application, which is a critical step towards this goal, is to understand the role of dendritic cells (DCs) in regulating vaccine-induced immunity against Q fever and identify which type of T cell response is more critical for vaccine-induced protective immunity. To achieve this objective, two specific aims were proposed to test the central hypothesis that C. burnetii phase I vaccine (PIV) and phase II vaccine (PIIV) differentially activate DCs, thereby promoting distinct T cell responses are responsible for the difference in their ability to confer protection. Aim 1 will determine the role of DCs in regulating vaccine-induced immunity against Q fever by examining i) if PIV and PIIV differentially activate DCs, thereby promoting distinct T cell differentiation patterns in a mouse model; and ii) if DCs play a role in vaccine-induced protection against C. burnetii aerosol infection in vivo. Aim 2 will determine the role of CD4+ T cell subsets in PIV-induced protective immunity against C. burnetii aerosol infection by using a mouse model to investigate i) if PIV- and PIIV-induced T cell responses are responsible for the difference in their ability to confer protection; and ii) which CD4+ subset T cell response is more critical for PIV-induced protection. As an outcome of this research, it will gain novel information for understanding the role of DCs in regulating T cell-mediated immunity and determining the role of T cell responses in vaccine-induced protective immunity against C. burnetii infection. This is expected to have significant positive effects on publich health, because it will provide critical information for developing a safe and effective vaccine against Q fever.