Iron regulation of chronic Toxoplasma gondii infection and immunity

弓形虫（Toxoplasma gondii）引起急性感染，其特征在于复制速殖子， 最终发展为慢性感染，其特征为持续的缓殖子期弓形虫囊肿， 大脑和中枢神经系统。慢性弓形虫感染影响约30%的美国人 在免疫缺陷期间，囊肿重新激活并引起严重的弓形虫脑炎。那里 目前还没有药物或治疗，有效地防止囊肿的发展或消除囊肿， 慢性感染者。弓形虫包囊发育、再活化和宿主的生物学基础 对急性和慢性感染免疫控制仍然知之甚少。从目前的证据和初步的 数据，我们假设铁的可用性调节寄生虫分化，包囊再激活， CD8+ T细胞免疫应答在控制急性感染和预防囊肿中的有效性 重新激活在目的1中，我们将研究弓形虫铁调节蛋白的铁感应作用， 分化和包囊再活化。在目标2中，我们将研究铁的可用性在发展中的作用。 CD8+ T细胞介导的免疫和慢性囊肿的控制中的CD8+ T细胞。这两个具体目标 将测试我们的新假设，即铁调节寄生虫阶段分化和宿主免疫急性和慢性感染。 慢性感染这些高影响力的实验预计将确定关键的铁调节机制， 作用于寄生虫和宿主，以控制分化、再活化和宿主免疫控制， 感染这些研究针对的是目前知识方面的重大差距，这些差距是取得进展的主要障碍， 外地

Toxoplasma gondii (Toxoplasma) causes an acute infection characterized by replicating tachyzoites that eventually develops into a chronic infection characterized by persisting bradyzoite stage Toxoplasma cysts in the brain and central nervous system. Chronic Toxoplasma infection affects ~30% of the United States population and during immune deficiency cysts reactivate and cause a severe Toxoplasmic encephalitis. There are currently no drugs or therapies that are effective at preventing cyst development or eliminating cysts in chronically infected individuals. The biology underpinning Toxoplasma cyst development, reactivation, and host immune control of acute and chronic infection is still poorly understood. From current evidence and preliminary data, we hypothesize that iron availability regulates parasite differentiation, cyst reactivation, and the effectiveness of the CD8+ T cell immune response in controlling acute infection and in preventing cyst reactivation. In Aim 1 we will investigate the role of iron sensing by the Toxoplasma Iron Regulatory Protein in differentiation and cyst reactivation. In Aim 2 we will investigate the role of iron availability in the development of CD8+ T cell mediated immunity and in the control of chronic cysts by CD8+ T cells. These two specific aims will test our novel hypothesis that iron regulates parasite stage differentiation and host immunity to acute and chronic infection. These high impact experiments are expected to define key iron regulated mechanisms that act on the parasite as well as the host to control differentiation, reactivation, and host immune control of infection. These studies address significant current gaps in knowledge that are major barriers to progress in the field.