Equipment Supplement request for a BD LSR Fortessa Flow Cytometer

BD LSR Fortessa 流式细胞仪的设备补充请求

基本信息

  • 批准号:
    9275190
  • 负责人:
  • 金额:
    $ 12.74万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-04-01 至 2020-01-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): This application is submitted under the NIH multiple PI initiative (http://grants.nih.gov/grants/guide/notice- files/NOT-OD-11-118.html). Drs. Ed Sherwood and David Williams with serve as the PIs. The multiple PI strategy is advantageous because it enables a "team science" approach that will draw equally on the expertise and experience of both of the PIs as well as their respective institutions. The critically ill patient frequently develops a complex disease spectrum that may include acute respiratory distress syndrome, systemic inflammatory response syndrome, sepsis syndrome, septic shock and/or multiple organ dysfunction syndrome. In the United States ~951,000 patients/year develop sepsis with approximately half of these patients in the ICU. The overall mortality rate is 28.6%. Those patients that survive the initial septic event may ultimately succumb to widespread organ dysfunction that can be either acute, due to hyper-inflammatory responses, or more prolonged due to immune dysfunction. It is well accepted that sepsis causes suppression of the immune system and that sepsis-induced immunoparalysis predisposes the critically ill patient to secondary infections. Attempts at developing effective therapies to prevent or treat sepsis and its associated immunosuppression have proven to be exceedingly difficult. In fact, no drugs are currently approved by the FDA for the management of sepsis. Recent data have provided compelling evidence that the innate immune system can be "trained" to respond more rapidly and effectively to pathogens following treatment with Dectin-1 agonists. We have successfully synthesized Dectin-1 ligands that increase resistance to sepsis. In this application, we propose the novel concept that it may be possible to "train" the compromised immune system with synthetic Dectin-1 ligands, such that an effective response can be mounted to existing and/or subsequent infections. We hypothesize that "immunologic training and metabolic reprogramming will decrease septic morbidity and mortality in clinically relevant models of sepsis and augment host immunity in vulnerable populations". To critically evaluate this hypothesis, we propose the following specific aims. Aim 1. Determine the effects of immune training on sequelae and outcomes in CLP-induced polymicrobial sepsis. This aim will define the efficacy of immune training in murine model of polymicrobial sepsis. Specifically, this aim wil determine if synthetic Dectin-1 agonists can "train" the immune system to prevent and/or treat polymicrobial sepsis. Aim 2. Determine the effect of immune training on sequelae and outcomes in a clinically relevant model of post-burn immunosuppression. This aim will establish whether training will improve survival in clinically relevant model of post-burn immunosuppression. Aim 3. Establish the impact of training on innate immune parameters in sepsis. This aim will define the alterations in innate immune function by which training augments the host response to infection. Aim 4. Define the mechanisms by which synthetic Dectin-1 ligands induce trained immunity. This aim will define the specific signaling alterations by which immune training enhances antimicrobial responses in populations that are at high risk of developing infections.
 描述(由申请人提供):本申请是根据NIH多重PI倡议(http://www.example.com files/NOT-OD-11-118.html)提交的。grants.nih.gov/grants/guide/notice-艾德舍伍德和大卫威廉姆斯博士担任PI。多个PI战略是有利的,因为它实现了“团队科学”的方法,将平等地利用两个PI及其各自机构的专业知识和经验。重症患者经常发展为复杂的疾病谱,可能包括急性呼吸窘迫综合征、全身炎症反应综合征、脓毒症综合征、脓毒性休克和/或多器官功能障碍综合征。在美国,每年约有951,000例患者发生脓毒症,其中约一半患者在ICU中。总死亡率为28.6%。那些在最初的脓毒症事件中存活下来的患者可能最终死于广泛的器官功能障碍,这些器官功能障碍可能是急性的,由于过度炎症反应,或由于免疫功能障碍而延长。普遍认为脓毒症会抑制免疫系统,脓毒症诱导的免疫麻痹使危重患者易于继发感染。事实证明,尝试开发有效的疗法来预防或治疗脓毒症及其相关的免疫抑制是极其困难的。事实上,目前FDA还没有批准任何药物用于治疗败血症。最近的数据已经提供了令人信服的证据,即先天免疫系统可以被“训练”以在用Dectin-1激动剂治疗后更快速和有效地对病原体作出反应。我们已经成功地合成了Dectin-1配体,其增加了对脓毒症的抵抗力。在本申请中,我们提出了一个新概念,即有可能用合成的Dectin-1配体“训练”受损的免疫系统,以便对现有和/或后续感染产生有效的反应。我们假设“免疫训练和代谢重编程将降低脓毒症临床相关模型的脓毒症发病率和死亡率,并增强易感人群的宿主免疫力”。为了批判性地评估这一假设,我们提出了以下具体目标。目标1。确定免疫训练对CLP诱导的多微生物脓毒症后遗症和结局的影响。该目的将确定免疫训练在多微生物脓毒症小鼠模型中的功效。具体地,该目的将确定合成的Dectin-1激动剂是否可以“训练”免疫系统以预防和/或治疗多微生物败血症。目标二。在烧伤后免疫抑制的临床相关模型中确定免疫训练对后遗症和结局的影响。这一目标将确定训练是否会提高烧伤后免疫抑制的临床相关模型的生存率。目标3。确定训练对脓毒症先天免疫参数的影响。这一目标将确定先天免疫功能的改变,通过这种改变,训练增强了宿主对感染的反应。目标4。定义合成Dectin-1配体诱导训练免疫的机制。这一目标将定义特定的信号改变,免疫训练通过这种改变增强感染高危人群的抗菌反应。

项目成果

期刊论文数量(0)
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专利数量(0)

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EDWARD R SHERWOOD其他文献

EDWARD R SHERWOOD的其他文献

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{{ truncateString('EDWARD R SHERWOOD', 18)}}的其他基金

Macrophage mitochodrial reprogramming and innate immune memory
巨噬细胞线粒体重编程和先天免疫记忆
  • 批准号:
    10550138
  • 财政年份:
    2020
  • 资助金额:
    $ 12.74万
  • 项目类别:
Macrophage mitochodrial reprogramming and innate immune memory
巨噬细胞线粒体重编程和先天免疫记忆
  • 批准号:
    10333362
  • 财政年份:
    2020
  • 资助金额:
    $ 12.74万
  • 项目类别:
Training Innate Immunity: A new approach to the treatment of Sepsis
训练先天免疫:治疗脓毒症的新方法
  • 批准号:
    10296894
  • 财政年份:
    2016
  • 资助金额:
    $ 12.74万
  • 项目类别:
Training Innate Immunity: A new approach to the treatment of Sepsis
训练先天免疫:治疗脓毒症的新方法
  • 批准号:
    10461115
  • 财政年份:
    2016
  • 资助金额:
    $ 12.74万
  • 项目类别:
Equipment supplement to "Training Innate Immunity: A new approach to the treatment of sepsis"
《训练先天免疫:治疗脓毒症的新方法》的设备补充
  • 批准号:
    10794766
  • 财政年份:
    2016
  • 资助金额:
    $ 12.74万
  • 项目类别:
Training Innate Immunity: A new approach to the treatment of Sepsis
训练先天免疫:治疗脓毒症的新方法
  • 批准号:
    10669060
  • 财政年份:
    2016
  • 资助金额:
    $ 12.74万
  • 项目类别:
Resistance of Beta 2 Microglobulin Null Mice to Sepsis
Beta 2 微球蛋白无效小鼠对脓毒症的抵抗力
  • 批准号:
    7256520
  • 财政年份:
    2003
  • 资助金额:
    $ 12.74万
  • 项目类别:
Resistance of Beta 2 Microglobulin Null Mice to Sepsis
Beta 2 微球蛋白无效小鼠对脓毒症的抵抗力
  • 批准号:
    7811704
  • 财政年份:
    2003
  • 资助金额:
    $ 12.74万
  • 项目类别:
Resistance of Beta 2 Microglobulin Null Mice to Sepsis
Beta 2 微球蛋白无效小鼠对脓毒症的抵抗力
  • 批准号:
    8578744
  • 财政年份:
    2003
  • 资助金额:
    $ 12.74万
  • 项目类别:
Resistance of Beta 2 Microglobulin Null Mice to Sepsis
Beta 2 微球蛋白无效小鼠对脓毒症的抵抗力
  • 批准号:
    8292209
  • 财政年份:
    2003
  • 资助金额:
    $ 12.74万
  • 项目类别:

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