Filtering of disseminating Cryptococcus neoformans out of vasculature

将传播的新型隐球菌从脉管系统中过滤出来

基本信息

  • 批准号:
    9387721
  • 负责人:
  • 金额:
    $ 19万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-05-19 至 2019-04-30
  • 项目状态:
    已结题

项目摘要

Project Summary Cryptococcosis is an opportunistic infection that occurs in immunocompromised individuals including AIDS patients, organ transplant recipients, cancer patients, and those treated with immunosuppressive therapies. It is estimated there are one million cases of cryptococcosis and proximately 600,000 deaths worldwide annually. The infection starts in the lung via inhalation of the encapsulated fungus Cryptococcus neoformans. However, the major and most lethal complication of cryptococcosis is meningoencephalitis. To cause meningoencephalitis, C. neoformans must disseminate from the lung and enter the bloodstream. As such, fungemia, detected frequently in AIDS patients during cryptococcosis, is believed to be one of the most critical steps in the development and persistence of cryptococcal meningoencephalitis. However, little is known about intravascular clearance of the disseminating C. neoformans due to technical challenge for in vivo studies. In particular, a critical gap in our understanding remains: Does a mechanism exist to actively eliminate disseminating C. neoformans out of vasculature, and what is the mechanism? Liver is situated at a confluence of arterial and venous blood. Kupffer cells (KCs) constitute ~90% of the tissue macrophages in the whole body and account for ~15% of the total liver cell population. CRIg, a unique complement receptor, has been recently identified on KCs of humans and animals. Although the liver is not a target organ of cryptococcosis, we hypothesize, based on our preliminary data, that KCs play a critical role in filtering of disseminating C. neoformans out of circulation via a mechanism involving complement receptor CRIg. We will test the hypothesis by addressing the following aims using intravital microscopy and other advanced approaches: (1) To characterize the role of KCs in filtering C. neoformans out of vasculature; (2) To dissect the mechanism(s) involved in capture of disseminating C. neoformans by KCs. The findings from this study will suggest that a therapeutic strategy aimed at enhancing macrophage recruitment and activity in the liver could help reducing the risk of cryptococcal meningocephalitis in AIDS patients.
项目摘要 隐球菌病是一种机会性感染,发生在免疫功能低下的个人 包括艾滋病患者、器官移植接受者、癌症患者以及接受过 免疫抑制疗法。据估计,有一百万例隐球菌病, 全世界每年约有60万人死亡。感染开始于肺部,通过吸入 包囊真菌新型隐球菌。然而,主要的和最致命的并发症, 隐球菌病是脑膜脑炎C.新型人必须传播 从肺部进入血液因此,在艾滋病患者中经常检测到的真菌血症, 隐球菌病,被认为是发展和持续的最关键的步骤之一, 隐球菌脑膜脑炎然而,关于血管内清除的知之甚少, 传播C.由于体内研究的技术挑战,特别是, 我们的理解仍然是:是否存在一种机制来积极消除传播C。新生 从脉管系统中分离出来,其机制是什么肝脏位于动脉和静脉的汇合处 血枯否细胞(KCs)占全身组织巨噬细胞的约90%, 约占总肝细胞群的15%。CRIg是一种独特的补体受体,最近已被鉴定为 人类和动物的KC。虽然肝脏不是隐球菌病的靶器官,但我们假设, 根据我们的初步数据,KCs在传播C.新生儿外出 通过涉及补体受体CRIg的机制。我们将通过以下方式来检验这一假设: 使用活体显微镜和其他先进方法实现以下目标:(1) 表征KC在过滤C中的作用。新生儿;(2)解剖机制 参与捕获传播C. KCs的新生儿这项研究的结果表明, 一种旨在增强肝脏中巨噬细胞募集和活性的治疗策略可能有助于 降低艾滋病患者患隐球菌脑膜炎的风险。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Meiqing Shi其他文献

Meiqing Shi的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Meiqing Shi', 18)}}的其他基金

Interactions of Cryptococcus neoformans with mononuclear phagocytes in the brain
新型隐球菌与大脑中单核吞噬细胞的相互作用
  • 批准号:
    10667732
  • 财政年份:
    2023
  • 资助金额:
    $ 19万
  • 项目类别:
Mechanisms of balancing the immune response during cryptococcal meningoencephalitis
隐球菌性脑膜脑炎期间平衡免疫反应的机制
  • 批准号:
    10761918
  • 财政年份:
    2023
  • 资助金额:
    $ 19万
  • 项目类别:
In vivo mechanisms of brain invasion by Cryptococcus neoformans
新型隐球菌脑侵袭的体内机制
  • 批准号:
    9912711
  • 财政年份:
    2017
  • 资助金额:
    $ 19万
  • 项目类别:
Brain dissemination of Cryptococcus neoformans mediated by neutrophils
中性粒细胞介导的新型隐球菌的脑传播
  • 批准号:
    8808266
  • 财政年份:
    2014
  • 资助金额:
    $ 19万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 19万
  • 项目类别:
    Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 19万
  • 项目类别:
    Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 19万
  • 项目类别:
    Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 19万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 19万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 19万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 19万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 19万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 19万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 19万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了