Cell Migration in the Infected Brain

受感染大脑中的细胞迁移

基本信息

  • 批准号:
    8450157
  • 负责人:
  • 金额:
    $ 32.09万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-09-01 至 2016-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Understanding the mechanisms that control inflammation in the CNS is critical to finding therapies for limiting damage to the brain from pathogens or neurodegenerative disease. Yet our knowledge is primarily limited to the adhesion molecules that facilitate entry to this site and not the factors that influence inflammatory cells once within the brain. Infection with the protozoan parasite Toxoplasma gondii leads to a chronic infection in the CNS with a continuous inflammatory response required in the brain to maintain latency. The absence of an appropriate immune response leads to the development of Toxoplasmic encephalitis (TE) and is therefore a common cause of AIDS related fatalities. Toxoplasma is an extremely common human infection, yet, in the immune- competent host there is no apparent pathology related to continuous inflammation in the brain. Thus, T. gondii infection leads to an immune response in the brain robust enough to provide protection against the parasite but sufficiently controlled to prevent immunopathology. A hypothesis being examined in our lab is that during chronic infection, cell migration can be guided in the brain by chemokine networks thereby controlling infection and limiting tissue damage. Recent studies of ours have demonstrated that following Toxoplasma infection, the presence of a reticular network is formed on which T cells migrate within the parenchyma of the brain. In addition, the chemokines CCL19 and CCL21 are significantly upregulated with cables of CCL21 associated with migrating T cells. These chemokines, known for their role in T cell and dendritic cell migration in the periphery, have not been well studied in the context of migration within the CNS. Experiments will be conducted to test the hypothesis that increased expression of CCL19/CCL21 in the infected brain is a mechanism to guide leukocytes within the brain parenchyma to control infection. Understanding how peripheral cells are directed to the site of infection and still prevent immunopathology in the CNS has direct relevance to controlling the multiple infectious pathogens that affect the brain. In addition, it may also lead to novel mechanisms to manipulate a pathological or deficient immune response in the CNS.
描述(由申请人提供):了解控制CNS炎症的机制对于寻找限制病原体或神经退行性疾病对大脑损伤的治疗至关重要。然而,我们的知识主要限于促进进入该部位的粘附分子,而不是影响大脑内炎症细胞的因素。原生动物寄生虫弓形虫的感染会导致中枢神经系统的慢性感染,大脑中需要持续的炎症反应来维持潜伏期。缺乏适当的免疫应答导致弓形虫脑炎(TE)的发展,因此是艾滋病相关死亡的常见原因。弓形虫是一种非常常见的人类感染,然而,在免疫活性宿主中,没有与脑中的持续炎症相关的明显病理。因此,T.弓形虫感染导致大脑中的免疫反应足够强以提供针对寄生虫的保护,但又足够控制以防止免疫病理学。我们实验室正在研究的一个假设是,在慢性感染期间,细胞迁移可以通过趋化因子网络在大脑中引导,从而控制感染并限制组织损伤。我们最近的研究表明,弓形虫感染后,形成了一个网状网络,T细胞在脑实质内迁移。此外,趋化因子CCL 19和CCL 21被与迁移T细胞相关的CCL 21的缆线显著上调。已知这些趋化因子在外周T细胞和树突状细胞迁移中的作用,但尚未在CNS内迁移的背景下进行充分研究。将进行实验以检验以下假设:感染脑中CCL 19/CCL 21的表达增加是引导脑实质内白细胞控制感染的机制。了解外周细胞如何被引导到感染部位并仍然防止CNS中的免疫病理学与控制影响大脑的多种感染性病原体直接相关。此外,它还可能导致新的机制来操纵CNS中的病理性或缺陷性免疫应答。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Emma H Wilson其他文献

Dark side illuminated: imaging of Toxoplasma gondii through the decades
  • DOI:
    10.1186/1756-3305-6-334
  • 发表时间:
    2013-11-22
  • 期刊:
  • 影响因子:
    3.500
  • 作者:
    Kathryn E McGovern;Emma H Wilson
  • 通讯作者:
    Emma H Wilson

Emma H Wilson的其他文献

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{{ truncateString('Emma H Wilson', 18)}}的其他基金

16th International Congress on Toxoplasmosis
第十六届国际弓形虫病大会
  • 批准号:
    10469179
  • 财政年份:
    2022
  • 资助金额:
    $ 32.09万
  • 项目类别:
The Role of SPARC during Toxoplasma infection in the Brain
SPARC 在大脑弓形虫感染过程中的作用
  • 批准号:
    8230524
  • 财政年份:
    2011
  • 资助金额:
    $ 32.09万
  • 项目类别:
Cell Migration in the Infected Brain
受感染大脑中的细胞迁移
  • 批准号:
    8636501
  • 财政年份:
    2011
  • 资助金额:
    $ 32.09万
  • 项目类别:
The Role of SPARC during Toxoplasma infection in the Brain
SPARC 在大脑弓形虫感染过程中的作用
  • 批准号:
    8114515
  • 财政年份:
    2011
  • 资助金额:
    $ 32.09万
  • 项目类别:
Cell Migration in the Infected Brain
受感染大脑中的细胞迁移
  • 批准号:
    8321461
  • 财政年份:
    2011
  • 资助金额:
    $ 32.09万
  • 项目类别:
Cell Migration in the Infected Brain
受感染大脑中的细胞迁移
  • 批准号:
    8236733
  • 财政年份:
    2011
  • 资助金额:
    $ 32.09万
  • 项目类别:

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