Mapping Immune Responses to CMV in Renal Transplant Recipients

总体：肾移植受者对CMV的免疫应答图谱 总结/摘要 巨细胞病毒（CMV）是疱疹病毒家族的一员，已经与人类一起进化了数千年。 潜伏期、免疫逃避和传播的复杂平衡。而高达70%的人类 世界范围内有证据表明CMV感染和血清阳性率接近100%，在某些地区，健康 人们几乎没有表现出原发性感染的临床症状。CMV疾病在免疫系统中很少观察到。 由于先天免疫应答和自然杀伤细胞（NK）和T细胞的持续监视， 协同控制CMV的细胞。然而，CMV是世界上最有问题的病原体之一。 免疫功能低下的宿主，在实体器官和干细胞移植后导致移植风险增加 功能障碍、死亡率和移植物丢失。我们建议研究CMV的先天性和适应性免疫应答 在使用高通量系统生物学方法的免疫受损实体器官移植接受者中， 精心策划的临床表型和新的统计和计算方法，以： 和适应性免疫反应，并确定CMV感染对免疫功能的影响。 同种免疫应答和移植排斥的发展; B）确定NK细胞在CMV中的作用 c）确定CMV感染对CMV再激活和慢性移植排斥的影响， 慢性同种异体移植物损伤拟议研究的长期目标是开发一个详细的分子图谱， 原发性和潜伏性CMV感染中先天性和适应性免疫应答之间的相互作用， 移植受体深入了解病毒与免疫系统的相互作用， 更充分的疫苗策略的概念，CMV感染的风险评估，以更好地了解 免疫系统，并确定CMV感染和器官移植损伤的相互作用。

OVERALL: Mapping Immune Reponses to CMV in Renal Transplant Recipients SUMMARY/ABSTRACT Cytomegalovirus (CMV), a member of the Herpes virus family, has evolved alongside humans for thousands of years with a complex balance of latency, immune evasion, and transmission. While up to 70% of humans worldwide have evidence of CMV infection and seroprevalence approaches 100% in certain areas, healthy people show little to no clinical symptoms of primary infection. CMV disease is rarely observed in immune competent hosts because of innate immune responses and constant surveillance by natural killer (NK) and T cells that cooperatively control CMV. However, CMV is one of the most problematic pathogens in the immunocompromised host, after solid organ and stem cell transplantation causing increased risk of graft dysfunction, mortality and graft loss. We propose to study the innate and adaptive immune responses to CMV in immunocompromised solid organ transplant recipients using a high-throughput systems biology approach, carefully curated clinical phenotypes and novel statistical and computational approaches to: a) profile innate and adaptive immune responses during primary CMV infection and define the effects of CMV infection on the development of alloimmune responsiveness and transplant rejection; b) determine the role of NK cells in CMV reactivation and chronic transplant rejection and c) define the effects of CMV infection on the development of chronic allograft injury. The long-term goal of the proposed research is to develop a detailed molecular map of the cross-talk between the innate and adaptive immune response in primary and latent CMV infection in the transplant recipient. Detailed insights into the interaction of the virus with the immune system stand to generate concepts for more adequate vaccine strategies, risk assessment for CMV infection to better understand the immune system and to define the interplay of CMV infection and organ transplant injury.