Iron regulation of chronic Toxoplasma gondii infection and immunity
铁对慢性弓形虫感染和免疫的调节
基本信息
- 批准号:10362711
- 负责人:
- 金额:$ 21.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-02 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:3&apos Untranslated RegionsAconitate HydrataseAcquired Immunodeficiency SyndromeAcuteAddressAffectBindingBiologyBrainCD8-Positive T-LymphocytesCell physiologyCellsCellular ImmunityCessation of lifeChronicCystDataDevelopmentEffectivenessEnterocytesExhibitsFrequenciesGene ExpressionGene ProteinsGenesGenetic TranscriptionGranzymeHospitalizationImmuneImmune responseImmunityIn VitroInbred BALB C MiceIndividualInfectionInfection ControlInterferon Type IIIronIron-Regulatory ProteinsKnowledgeMessenger RNAMissionMitochondriaMolecularMorbidity - disease rateMusNeuraxisNeuronsNutrientOocystsOral IngestionParasitesPharmaceutical PreparationsPopulationProteinsPublic HealthRegulationResponse ElementsRoleSignal TransductionStressT cell responseT-LymphocyteTFRC geneTestingToxoplasmaToxoplasma gondiiToxoplasmosisUnited StatesUnited States National Institutes of Healthacute infectioncell mediated immune responsecell typechronic infectionexperimental studyfoodborne pathogenimprovedin vivoiron deficiencynovelpreventtoxoplasmic encephalitis
项目摘要
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.
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
对急性和慢性感染的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
项目成果
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{{ truncateString('DAVID J BZIK', 18)}}的其他基金
Metabolic basis for the persistence of dormant Toxoplasma gondii infection
休眠弓形虫感染持续存在的代谢基础
- 批准号:
10562309 - 财政年份:2022
- 资助金额:
$ 21.91万 - 项目类别:
Glucosylation Regulates Cyst Wall Formation, Stability, and Persistence of the AIDS Pathogen Toxoplasma gondii
糖基化调节艾滋病病原体弓形虫的囊壁形成、稳定性和持久性
- 批准号:
10493386 - 财政年份:2021
- 资助金额:
$ 21.91万 - 项目类别:
Glucosylation Regulates Cyst Wall Formation, Stability, and Persistence of the AIDS Pathogen Toxoplasma gondii
糖基化调节艾滋病病原体弓形虫的囊壁形成、稳定性和持久性
- 批准号:
10334999 - 财政年份:2021
- 资助金额:
$ 21.91万 - 项目类别:
Intravacuolar network dense granule protein biology in chronic Toxoplasma infection
慢性弓形虫感染中的液泡内网络致密颗粒蛋白生物学
- 批准号:
10084815 - 财政年份:2020
- 资助金额:
$ 21.91万 - 项目类别:
Novel vacuole biology in chronic Toxoplasma infection
慢性弓形虫感染中的新型液泡生物学
- 批准号:
10092083 - 财政年份:2020
- 资助金额:
$ 21.91万 - 项目类别:
Intravacuolar network dense granule protein biology in chronic Toxoplasma infection
慢性弓形虫感染中的液泡内网络致密颗粒蛋白生物学
- 批准号:
10010660 - 财政年份:2020
- 资助金额:
$ 21.91万 - 项目类别:
Dense granule protein virulence factors in Toxoplasma gondii infection
弓形虫感染中的致密颗粒蛋白毒力因子
- 批准号:
8730970 - 财政年份:2014
- 资助金额:
$ 21.91万 - 项目类别:
Parasite secreted proteins control host response to Toxoplasma gondii infection
寄生虫分泌的蛋白质控制宿主对弓形虫感染的反应
- 批准号:
8466449 - 财政年份:2013
- 资助金额:
$ 21.91万 - 项目类别:
Parasite secreted proteins control host response to Toxoplasma gondii infection
寄生虫分泌的蛋白质控制宿主对弓形虫感染的反应
- 批准号:
8605518 - 财政年份:2013
- 资助金额:
$ 21.91万 - 项目类别:
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