CUTANEOUS IMMUNITY IN LYME DISEASE

莱姆病的皮肤免疫

• 批准号: 8358164
• 负责人: MONICA E EMBERS
• 金额: $ 3.72万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358164
• 关键词: Antigen-Presenting Cells; Antigens; Bite; Borrelia burgdorferi; Cellular Immunity; Cutaneous; Dendritic Cells; Diagnosis; Funding; Grant; Immune response; Immunity; Immunization; Infection; Ixodes; Lyme Disease; Modeling; Mus; National Center for Research Resources; Nature; Order Spirochaetales; Prevention; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Route; Saliva; Salivary; Site; Skin; Source; Ticks; United States National Institutes of Health; Vaccination; Vector-transmitted infectious disease; cost; feeding; in vivo; lymph nodes; migration; monocyte; response; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The systemic spread and protean nature of Lyme disease lends to difficult diagnosis and often prolonged illness. Vaccination remains the best means of control. Transmission of the Borrelia burgdorferi (Bb) spirochete is through the bite of an Ixodes sp. tick. Those who have been infected are neither impervious to a subsequent tick bite nor to reinfection, so immunity to tick salivary components and Bb antigens are insufficient for protection. Tick saliva possesses components responsible for modulation of the immune response, which may contribute to meager immunity to subsequent infection. The immune response at the site of tick feeding and infection, specifically which is proffered by the antigen-presenting cells (APCs) in skin, is the subject of this project. Though the skin is the natural route of infection, immunization against Bb has been focused exclusively in the parenteral routes. The central hypotheses are that tick saliva modulates cutaneous responses that impair primary cell-mediated immunity (CMI) and that priming APCs in skin with a Bb immunogen can diminish this inhibition. We have shown that the activation of monocytes in response to Bb is significantly dampened by tick saliva. Yet, the primary response in the skin and subsequent impact on CMI has not been explored. Specific aim (SA)1 will be to define the immunomodulatory effects of tick saliva on the immune response generated in skin against Bb using a murine ex vivo model. SA2 will be to assess, in vivo, the impact of tick saliva on activation and migration of dendritic cells from the skin to the lymph nodes in response to antigen. SA3 will be to utilize an appropriate Bb antigen (DbpA) to prime the immune response in the skin and evaluate both ex vivo and in vivo, the impact on immunity against tick-transmitted Bb. These studies have the potential to impact our understanding and possible prevention of not only Lyme disease, but other vector-borne diseases as well.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 莱姆病的系统性传播和多变的性质导致难以诊断和经常长期患病。接种疫苗仍然是最好的控制手段。伯氏疏螺旋体（Bb）螺旋体的传播是通过硬蜱属蜱叮咬。 那些已经被感染的人既不抵抗随后的蜱叮咬，也不抵抗再次感染，因此对蜱唾液成分和Bb抗原的免疫力不足以保护。 蜱的唾液具有调节免疫反应的成分，这可能导致对随后感染的免疫力低下。蜱虫取食和感染部位的免疫应答，特别是皮肤中的抗原呈递细胞（APC）提供的免疫应答，是本项目的主题。虽然皮肤是感染的自然途径，但针对Bb的免疫接种仅集中在肠胃外途径。 中心假设是，蜱唾液调节皮肤的反应，损害初级细胞介导的免疫（CMI），并在皮肤中的抗原提呈细胞与Bb免疫原可以减少这种抑制。 我们已经表明，响应于Bb的单核细胞的激活被蜱唾液显著抑制。然而，皮肤的主要反应和随后对CMI的影响尚未探讨。具体目标（SA）1将是使用鼠离体模型确定蜱唾液对皮肤中产生的抗Bb免疫应答的免疫调节作用。SA 2将在体内评估蜱唾液对树突状细胞响应抗原从皮肤到淋巴结的活化和迁移的影响。 SA 3将利用适当的Bb抗原（DbpA）引发皮肤中的免疫应答，并评价离体和体内对蜱传播Bb免疫力的影响。这些研究有可能影响我们对莱姆病以及其他病媒传播疾病的理解和可能的预防。