Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection

SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用

基本信息

  • 批准号:
    10468025
  • 负责人:
  • 金额:
    $ 42.49万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-09-20 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT This application proposes to interrogate how the divalent cation transporter NRAMP1/SLC11A1 mediates control of infection with bacterial pathogens. While the function of this transporter has been studied in macrophages, our studies on the link between vitamin A deficiency and susceptibility to Salmonella bacteremia uncovered an unsuspected role for NRAMP1/SLC11A1 in control of systemic S. Typhimurium infection by neutrophils. This finding goes against the conventional wisdom that SLC11A1-dependent host defenses are associated exclusively with macrophages. If true, this would be a novel concept and would represent a major advance in understanding both the role of SLC11A1 and neutrophil function. The long-term goal of this proposed work is to uncover novel mechanisms by which phagocytes control disseminated infections. We propose that a functional difference in neutrophils expressing mutant SLC11A1, as a result of impaired bactericidal mechanisms, increases susceptibility of SLC11A1-deficient mice to pathogens. Our central hypothesis is that SLC11A1 function promotes the bactericidal activity of neutrophils. We will test our hypothesis using the complementary approaches outlined in the following specific aims: (1) Define cell neutrophil-specific functions of SLC11A1 in controlling systemic salmonellosis. (2) Determine the mechanistic basis for SLC11A1 function in neutrophil antimicrobial activity. (3) Define how SLC11A1 promotes neutrophil-mediated disease pathology. Our proposed work is novel and innovative in that the function of SLC11A1 in cell types other than macrophages is not yet known. We will test our hypotheses on the role of SLC11A1 in neutrophils in a rigorous manner and with multiple complementary lines of experimentation. This work is significant in that understanding the role of SLC11A1 in the neutrophil will shed light on how neutrophils control disseminated Salmonella infection, and the results are likely to open the door to studies the role of neutrophils in controlling other pathogens, such as Leishmania and non-tuberculous mycobacteria, in which SLC11A1 function is important. It is our expectation that the results of this work will advance our fundamental understanding of neutrophil biology as well as providing tools and concepts to study the links between SLC11A1 and other infectious and autoimmune pathologies in which this transporter has been implicated.
摘要

项目成果

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Renee M Tsolis其他文献

Renee M Tsolis的其他文献

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{{ truncateString('Renee M Tsolis', 18)}}的其他基金

2023 Salmonella Biology and Pathogenesis Gordon Research Conference and Seminar
2023年沙门氏菌生物学与发病机制戈登研究会议暨研讨会
  • 批准号:
    10683617
  • 财政年份:
    2023
  • 资助金额:
    $ 42.49万
  • 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
  • 批准号:
    10224776
  • 财政年份:
    2019
  • 资助金额:
    $ 42.49万
  • 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
  • 批准号:
    10022095
  • 财政年份:
    2019
  • 资助金额:
    $ 42.49万
  • 项目类别:
2019 Microbial Adhesion and Signal Transduction GRC/GRS
2019微生物粘附与信号转导GRC/GRS
  • 批准号:
    9752745
  • 财政年份:
    2019
  • 资助金额:
    $ 42.49万
  • 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
  • 批准号:
    10683118
  • 财政年份:
    2019
  • 资助金额:
    $ 42.49万
  • 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
  • 批准号:
    10772361
  • 财政年份:
    2019
  • 资助金额:
    $ 42.49万
  • 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
  • 批准号:
    10755395
  • 财政年份:
    2019
  • 资助金额:
    $ 42.49万
  • 项目类别:
Systemic infections with non-typhoidal Salmonella
非伤寒沙门氏菌全身感染
  • 批准号:
    9238432
  • 财政年份:
    2016
  • 资助金额:
    $ 42.49万
  • 项目类别:
Detection of bacterial Type IV secretion by the unfolded protein response
通过未折叠蛋白反应检测细菌 IV 型分泌物
  • 批准号:
    8718850
  • 财政年份:
    2014
  • 资助金额:
    $ 42.49万
  • 项目类别:
Detection of bacterial Type IV secretion by the unfolded protein response
通过未折叠蛋白反应检测细菌 IV 型分泌物
  • 批准号:
    8874102
  • 财政年份:
    2014
  • 资助金额:
    $ 42.49万
  • 项目类别:

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New technologies for targeted delivery of anti-bacterial agents
抗菌药物靶向递送新技术
  • 批准号:
    1654774
  • 财政年份:
    2015
  • 资助金额:
    $ 42.49万
  • 项目类别:
    Studentship
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  • 批准号:
    8416313
  • 财政年份:
    2012
  • 资助金额:
    $ 42.49万
  • 项目类别:
Targeting bacterial phosphatases for novel anti-bacterial agents.
针对细菌磷酸酶的新型抗菌剂。
  • 批准号:
    8298885
  • 财政年份:
    2012
  • 资助金额:
    $ 42.49万
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