Oxidative killing of Pneumococcus

氧化杀死肺炎球菌

基本信息

  • 批准号:
    10116271
  • 负责人:
  • 金额:
    $ 22.65万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-03-01 至 2023-02-28
  • 项目状态:
    已结题

项目摘要

Streptococcus pneumoniae (Spn) is the main cause of community acquired pneumonia and meningitis in children and the elderly, and of septicemia in HIV patients. Boosting the function of host immune responses could offer novel intervention strategies against Spn. There is a critical gap in our knowledge to identify new, broad range, anti-Spn mechanisms of the respiratory innate immune system. Bronchial epithelial cells (BEC) are the primary responders to Spn infection. BECs orchestrate an oxidative extracellular antimicrobial system present in the airway surface liquid consisting of the protein lactoperoxidase (LPO), the thiocyanate anion (SCN-) and hydrogen peroxide (H2O2). LPO oxidizes SCN- using H2O2 into microbicidal hypothiocyanite (OSCN-). Dual oxidase 1 (Duox1), an NADPH oxidase protein highly expressed in the apical membrane of BECs, is the H2O2 source for the antimicrobial action of LPO. Our preliminary result show that the Duox1/LPO-based system efficiently kills several strains of Spn in different experimental systems. Our long-term goal is to determine whether the Duox1/LPO/SCN- antibacterial system could be manipulated in Spn infection for therapeutic purposes in humans. The objective of this proposal is to establish the anti-Spn role of the Duox1/LPO-based oxidative mechanism. Based on preliminary data our central hypothesis is that the Duox1/H2O2/LPO/SCN- system kills Spn bacteria in a strain-independent manner, attenuates infection and associated tissue damage in a mouse model of Spn lung infection. To test this hypothesis, our specific aims are to determine the mechanism of Spn killing by Duox1/LPO in vitro, to establish the in vivo role of Duox1 in Spn killing, and to explore whether therapeutic manipulation of the Duox1/LPO-based system attenuates Spn pneumonia in an animal model. The rationale for the proposed research is that we need to characterize how powerful the Duox1/LPO-based system is in fighting Spn to explore its therapeutical potential in humans in the future. It is anticipated that our aims will yield the following expected outcomes: 1) identification of the antibacterial mechanism of the Duox1/LPO-based system against Spn, 2) establishing the in vivo relevance of Duox1 in Spn infection; and 3) providing essential results on the therapeutic potential of the Duox1/LPO-based mechanism to attenuate Spn lung infection. Our innovative work shows that a unique antimicrobial system is powerful in killing Spn and explores a novel, nontraditional immune mechanism for its potential to be used against a major lung pathogen. In summary, our proposal will have a positive impact in the fields of airway epithelial and Spn biology, and general antibacterial innate immune responses by identifying Duox1 and LPO, as a novel, crucial, innate immune weapons of the respiratory innate immune system against Spn.
肺炎链球菌(Spn)是社区获得性肺炎的主要原因, 儿童和老年人的脑膜炎以及艾滋病毒患者的败血症。增强主机功能 免疫反应可以提供新的针对SPN的干预策略。在我们的研究中, 知识,以确定新的,广泛的,呼吸先天免疫系统的抗Spn机制。 支气管上皮细胞(BEC)是对Spn感染的主要应答者。BEC编排了一个 存在于由蛋白质组成的气道表面液体中的氧化性细胞外抗微生物系统 乳过氧化物酶(LPO)、硫氰酸根阴离子(SCN-)和过氧化氢(H2 O2)。LPO氧化SCN- 用H2 O2转化为杀微生物的次硫氰酸盐(OSCN-)。双氧化酶1(Duox 1),一种NADPH氧化酶 在BEC的顶膜中高度表达的蛋白质,是抗微生物作用的H2 O2来源 的LPO。我们的初步结果表明,基于Duox 1/LPO的系统有效地杀死了几种菌株, 在不同的实验系统中的Spn。我们的长期目标是确定Duox 1/LPO/SCN- 可以在人的Spn感染中操纵抗菌系统用于治疗目的。的 该提案的目的是建立基于Duox 1/LPO的氧化机制的抗Spn作用。 基于初步数据,我们的中心假设是Duox 1/H2 O2/LPO/SCN-系统杀死Spn 以菌株非依赖性方式抑制细菌,减轻小鼠中的感染和相关组织损伤, Spn肺部感染模型。为了验证这一假设,我们的具体目标是确定 体外研究Duox 1/LPO对Spn的杀伤作用,建立Duox 1在体内对Spn的杀伤作用,并探讨Duox 1/LPO对Spn的杀伤作用。 Duox 1/LPO系统的治疗操作是否能减轻 动物模型这项研究的基本原理是,我们需要描述 基于Duox 1/LPO的系统正在与Spn作战,以探索其未来在人类中的治疗潜力。 预计我们的目标将产生以下预期成果:1)识别 Duox 1/LPO系统对Spn的抗菌机制,2)建立体内 Duox 1在Spn感染中的相关性;以及3)提供关于Duox 1治疗潜力的基本结果。 Duox 1/LPO为基础的机制,以减轻SPN肺部感染。我们的创新工作表明, 抗微生物系统在杀死Spn方面是强大的,并探索了一种新的非传统免疫机制 因为它有可能被用于对抗一种主要的肺部病原体。总的来说,我们的建议将具有积极意义。 在气道上皮和Spn生物学以及一般抗菌先天免疫领域的影响 通过识别Duox 1和LPO作为呼吸道疾病的一种新型,关键的先天免疫武器, 先天性免疫系统对Spn。

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 }}

Balazs Rada其他文献

Balazs Rada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('Balazs Rada', 18)}}的其他基金

Association of Staphylococcus aureus infection with autoimmunity in cystic fibrosis
金黄色葡萄球菌感染与囊性纤维化自身免疫的关系
  • 批准号:
    10226644
  • 财政年份:
    2021
  • 资助金额:
    $ 22.65万
  • 项目类别:
Association of Staphylococcus aureus infection with autoimmunity in cystic fibrosis
金黄色葡萄球菌感染与囊性纤维化自身免疫的关系
  • 批准号:
    10353431
  • 财政年份:
    2021
  • 资助金额:
    $ 22.65万
  • 项目类别:
Dual oxidase and lactoperoxidase in influenza infection
流感感染中的双氧化酶和乳过氧化物酶
  • 批准号:
    10328261
  • 财政年份:
    2020
  • 资助金额:
    $ 22.65万
  • 项目类别:
Dual oxidase and lactoperoxidase in influenza infection
流感感染中的双氧化酶和乳过氧化物酶
  • 批准号:
    10556348
  • 财政年份:
    2020
  • 资助金额:
    $ 22.65万
  • 项目类别:
Dual oxidase and lactoperoxidase in influenza infection
流感感染中的双氧化酶和乳过氧化物酶
  • 批准号:
    9981325
  • 财政年份:
    2020
  • 资助金额:
    $ 22.65万
  • 项目类别:
Neutrophil extracellular traps in cystic fibrosis
囊性纤维化中的中性粒细胞胞外陷阱
  • 批准号:
    10078969
  • 财政年份:
    2018
  • 资助金额:
    $ 22.65万
  • 项目类别:
Neutrophil extracellular traps in cystic fibrosis
囊性纤维化中的中性粒细胞胞外陷阱
  • 批准号:
    9898433
  • 财政年份:
    2018
  • 资助金额:
    $ 22.65万
  • 项目类别:
Neutrophil Extracellular Traps in Cystic Fibrosis
囊性纤维化中的中性粒细胞胞外陷阱
  • 批准号:
    9324418
  • 财政年份:
    2016
  • 资助金额:
    $ 22.65万
  • 项目类别:

相似国自然基金

湍流和化学交互作用对H2-Air-H2O微混燃烧中NO生成的影响研究
  • 批准号:
    51976048
  • 批准年份:
    2019
  • 资助金额:
    61.0 万元
  • 项目类别:
    面上项目

相似海外基金

RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 22.65万
  • 项目类别:
    Standard Grant
SBIR Phase I: High-Efficiency Liquid Desiccant Regenerator for Desiccant Enhanced Evaporative Air Conditioning
SBIR 第一阶段:用于干燥剂增强蒸发空调的高效液体干燥剂再生器
  • 批准号:
    2335500
  • 财政年份:
    2024
  • 资助金额:
    $ 22.65万
  • 项目类别:
    Standard Grant
Catalyzing Sustainable Air Travel: Unveiling Consumer Willingness to Pay for Sustainable Aviation Fuel through Information Treatment in Choice Experiment and Cross-Country Analysis
促进可持续航空旅行:通过选择实验和跨国分析中的信息处理揭示消费者支付可持续航空燃油的意愿
  • 批准号:
    24K16365
  • 财政年份:
    2024
  • 资助金额:
    $ 22.65万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
COMPAS: co integration of microelectronics and photonics for air and water sensors
COMPAS:微电子学和光子学的共同集成,用于空气和水传感器
  • 批准号:
    10108154
  • 财政年份:
    2024
  • 资助金额:
    $ 22.65万
  • 项目类别:
    EU-Funded
Simulating Urban Air Pollution In The Lab
在实验室模拟城市空气污染
  • 批准号:
    MR/Y020014/1
  • 财政年份:
    2024
  • 资助金额:
    $ 22.65万
  • 项目类别:
    Fellowship
Collaborative Research: Phenotypic and lineage diversification after key innovation(s): multiple evolutionary pathways to air-breathing in labyrinth fishes and their allies
合作研究:关键创新后的表型和谱系多样化:迷宫鱼及其盟友呼吸空气的多种进化途径
  • 批准号:
    2333683
  • 财政年份:
    2024
  • 资助金额:
    $ 22.65万
  • 项目类别:
    Continuing Grant
Collaborative Research: Phenotypic and lineage diversification after key innovation(s): multiple evolutionary pathways to air-breathing in labyrinth fishes and their allies
合作研究:关键创新后的表型和谱系多样化:迷宫鱼及其盟友呼吸空气的多种进化途径
  • 批准号:
    2333684
  • 财政年份:
    2024
  • 资助金额:
    $ 22.65万
  • 项目类别:
    Continuing Grant
CRII: CSR: Towards an Edge-enabled Software-Defined Vehicle Framework for Dynamic Over-the-Air Updates
CRII:CSR:迈向支持边缘的软件定义车辆框架,用于动态无线更新
  • 批准号:
    2348151
  • 财政年份:
    2024
  • 资助金额:
    $ 22.65万
  • 项目类别:
    Standard Grant
Development of a low-pressure loss air purification device using rotating porous media and a proposal for its use in ventilation systems
使用旋转多孔介质的低压损失空气净化装置的开发及其在通风系统中的使用建议
  • 批准号:
    24K17404
  • 财政年份:
    2024
  • 资助金额:
    $ 22.65万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
AIR QUALITY AND HEALTH IMPACT OF PRIMARY SEMI-VOLATILE AND SECONDARY PARTICLES AND THEIR ABATEMENT
一次半挥发性颗粒和二次颗粒对空气质量和健康的影响及其消除
  • 批准号:
    10100997
  • 财政年份:
    2024
  • 资助金额:
    $ 22.65万
  • 项目类别:
    EU-Funded
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了