Immune Responses to Schistosome Egg Antigens

对血吸虫卵抗原的免疫反应

基本信息

  • 批准号:
    7897825
  • 负责人:
  • 金额:
    $ 37.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-07-22 至 2012-06-30
  • 项目状态:
    已结题

项目摘要

Previously we demonstrated that schistosome egg glycans are largely responsible for parasite induced immunomodulation and Th2-biasing. We identified LNFPIII and LNnT as two glycans present on schistosome eggs that drive immune modulation in vifro and in vivo. These glycans induce immune suppression and CD4+ Th2-type responses when presented 10 antigen presenting cells as glyco-conjugales. The overall goal of this renewal application is to understand how defined schistosome glycans activate APCs in such a manner that these APCs drive anti-inflammatory responses. Alternative activation of human DCs by soluble egg antigens occurs through three Ctype lectins: mannose receptor (MR), macrophage galactose receptor (MgI) and DC-SIGN. LNFPIlI binds to each of these lectins and to MSIGNR1 . Therefore we will perform experiments in mice deficient in these lectins or use HEK cells singly transfected with these lectins to examine their roles in LNFPIII induced APC activation. In addition, by transfecting HEK cells expressing TLR4/CD14/MD2 with these same C-type lectins we will determine if activation of APes via these lectins alters Toll-like receptor induced signaling. Because C-type lectin-ligand interaction leads to endosome formation, we will examine the role endosome formation plays in alternative activation using inhibitors of endosome formation. We have performed microarray analysis to examine signaling pathways downstream of LNFPlIl activation and Identify candidate genes. We will use RT -PCR to validate several candidate genes and then siRNA to knockdown these genes to determine if their role is critical for alternative activation. For proteins we will use Rules Based Medicine (RBM) analysis to measure levels of >72 proteins known to be involved in innate activation of APCs. The specific aims are: 1) What roles do specific C-type lectins and endosome formation play in driving LNFPIII induction of alternative activation of APCs? 2) Determine if candidate signaling molecules and soluble factors are required for LNFPIII induced altemative activation of APCs?
以前,我们证明,卵囊体聚糖主要负责寄生虫诱导的免疫调节和Th 2偏置。我们将LNFP III和LNnT鉴定为存在于卵裂体卵上的两种聚糖,其驱动体外和体内免疫调节。当这些聚糖作为糖缀合物呈递给抗原呈递细胞时,其诱导免疫抑制和CD 4 + Th 2型应答。本更新申请的总体目标是了解定义的溶酶体聚糖如何以这些APC驱动抗炎反应的方式激活APC。可溶性卵抗原通过三种C型凝集素:甘露糖受体(MR)、巨噬细胞半乳糖受体(MgI)和DC-SIGN激活人DC。LNFPIII与这些凝集素中的每一种结合并与MSIGNR 1结合。因此,我们将在缺乏这些凝集素的小鼠中进行实验或使用单独转染这些凝集素的HEK细胞来检查它们在LNFP III诱导的APC活化中的作用。此外,通过用这些相同的C型凝集素刺激表达TLR 4/CD 14/MD 2的HEK细胞,我们将确定通过这些凝集素激活AP是否改变Toll样受体诱导的信号传导。由于C型凝集素-配体相互作用导致内体形成,我们将使用内体形成抑制剂研究内体形成在替代激活中的作用。我们已经进行了微阵列分析,以检查LNFPlIl激活的下游信号通路并鉴定候选基因。我们将使用RT-PCR来验证几个候选基因,然后使用siRNA来敲除这些基因,以确定它们的作用是否对替代激活至关重要。对于蛋白质,我们将使用基于规则的医学(RBM)分析来测量已知参与APC先天激活的>72种蛋白质的水平。具体目标是:1)特异性C型凝集素和内体形成在驱动LNFP III诱导APC的交替激活中起什么作用?2)确定候选信号分子和可溶性因子是否是LNFP III诱导的APC交替激活所必需的?

项目成果

期刊论文数量(14)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Dendritic cells activated by an anti-inflammatory agent induce CD4(+) T helper type 2 responses without impairing CD8(+) memory and effector cytotoxic T-lymphocyte responses.
抗炎剂激活的树突状细胞可诱导 CD4( ) T 辅助细胞 2 型反应,而不损害 CD8( ) 记忆和效应细胞毒性 T 淋巴细胞反应。
  • DOI:
    10.1111/j.1365-2567.2009.03193.x
  • 发表时间:
    2010
  • 期刊:
  • 影响因子:
    6.4
  • 作者:
    Wang,Yang;Da'Dara,AkramA;Thomas,PaulG;Harn,DonaldA
  • 通讯作者:
    Harn,DonaldA
Mito-DCA: a mitochondria targeted molecular scaffold for efficacious delivery of metabolic modulator dichloroacetate.
  • DOI:
    10.1021/cb400944y
  • 发表时间:
    2014-05-16
  • 期刊:
  • 影响因子:
    4
  • 作者:
    Pathak, Rakesh K.;Marrache, Sean;Harn, Donald A.;Dhar, Shanta
  • 通讯作者:
    Dhar, Shanta
Immune stimulating photoactive hybrid nanoparticles for metastatic breast cancer.
Ex vivo generation of functional immune cells by mitochondria-targeted photosensitization of cancer cells.
通过癌细胞的线粒体靶向光敏作用离体产生功能性免疫细胞。
Polarization of host immune responses by helminth-expressed glycans.
蠕虫表达的聚糖对宿主免疫反应的极化。
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Donald A Harn其他文献

Donald A Harn的其他文献

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{{ truncateString('Donald A Harn', 18)}}的其他基金

The Effect of Helminth Infection on HIV-1 Vaccines
蠕虫感染对 HIV-1 疫苗的影响
  • 批准号:
    7877043
  • 财政年份:
    2009
  • 资助金额:
    $ 37.42万
  • 项目类别:
The Effect of Helminth Infection on HIV-1 Vaccines
蠕虫感染对 HIV-1 疫苗的影响
  • 批准号:
    7418170
  • 财政年份:
    2009
  • 资助金额:
    $ 37.42万
  • 项目类别:
Effect of Helminth Infection on HIV-1 Vaccines
蠕虫感染对 HIV-1 疫苗的影响
  • 批准号:
    7923569
  • 财政年份:
    2008
  • 资助金额:
    $ 37.42万
  • 项目类别:
Effect of Helminth Infection on HIV-1 Vaccines
蠕虫感染对 HIV-1 疫苗的影响
  • 批准号:
    7760839
  • 财政年份:
    2008
  • 资助金额:
    $ 37.42万
  • 项目类别:
Effect of Helminth Infection on HIV-1 Vaccines
蠕虫感染对 HIV-1 疫苗的影响
  • 批准号:
    7494355
  • 财政年份:
    2008
  • 资助金额:
    $ 37.42万
  • 项目类别:
Effect of Helminth Infection on HIV-1 Vaccines
蠕虫感染对 HIV-1 疫苗的影响
  • 批准号:
    7565900
  • 财政年份:
    2008
  • 资助金额:
    $ 37.42万
  • 项目类别:
Effect of Helminth Infection on HIV-1 Vaccines
蠕虫感染对 HIV-1 疫苗的影响
  • 批准号:
    8013546
  • 财政年份:
    2008
  • 资助金额:
    $ 37.42万
  • 项目类别:
Effect of Helminth Infection on HIV-1 Vaccines
蠕虫感染对 HIV-1 疫苗的影响
  • 批准号:
    8213688
  • 财政年份:
    2008
  • 资助金额:
    $ 37.42万
  • 项目类别:
Prophylactic Vaccines for Schistosomiasis
血吸虫病预防疫苗
  • 批准号:
    7923601
  • 财政年份:
    2007
  • 资助金额:
    $ 37.42万
  • 项目类别:
Prophylactic Vaccines for Schistosomiasis
血吸虫病预防疫苗
  • 批准号:
    7782810
  • 财政年份:
    2007
  • 资助金额:
    $ 37.42万
  • 项目类别:

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开发作为抗炎剂和砷解毒剂的小分子抑制剂
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