Trained immunity and the regulation of anti-fungal defense

训练有素的免疫力和抗真菌防御的调节

基本信息

  • 批准号:
    10557883
  • 负责人:
  • 金额:
    $ 63.08万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-02-01 至 2027-01-31
  • 项目状态:
    未结题

项目摘要

Abstract: Although often overlooked as a significant health problem, pulmonary infections with fungal pathogens present a clinical problem of growing concern. Aspergillus fumigatus (Af) and Cryptococcus neoformans (Cn) are two clinically important fungal pathogens that affect immunosuppressed patients worldwide. Both infections are difficult to treat and are associated with high mortality rates. A better understanding of immune mechanisms of host defense against fungi hold the promise of providing the basis for the future development of novel, immune based interventions to improve patient outcomes. Pulmonary macrophages are critical, front-line mediators of host protection against fungi and other pulmonary pathogens. Despite the well-defined role of lung macrophages as crucial initiators of immunity to diverse sets of pathogens, our understanding of how previous infection history shapes subsequent macrophage responses to fungal infection in the lung remain poorly defined. Moreover, an emerging body of literature has now revealed that macrophage populations in the lung are more heterogeneous than originally appreciated and can undergo innate training; an enhanced response to diverse secondary challenges. It is now also understood that alveolar macrophages present in the lung can originate from embryonic precursors (tissue-derived alveolar macrophages-TD-AMs) or from blood monocytes (monocyte-derived alveolar macrophages-Mo-AMs). Whether TD-AM and Mo-AM are equally capable of undergoing innate training is currently unclear. It is also unknown whether innate training is a conserved response to any infectious stimuli or regulated by specific pathways. In preliminary studies, we uncovered that priming with an immunogenic strain of Cn (HK-fbp1) could confer heterologous protection against infection with Af even in the context of drug-induced immunosuppression and in a T cell-independent manner. Preliminary data gathered, suggest that neutrophils and STAT1-dependent signals are important regulators of antifungal monocytes and their differentiation into monocyte-derived cells. Based on our aggregate observations, the central hypothesis of this project is that: CCR2+mo are critical mediators of antifungal immunity and can be instructed by HK-fbp1 into trained mo-AM via the coordinated actions of neutrophils and an interferon (IFN) cascade. We will address two related but independent aims: Aim 1: Investigate the impact of HK-fbp1 immunization to pulmonary innate cell priming and training to promote antifungal immunity; Aim 2: Decipher the contributions of neutrophils in the regulation of antifungal trained immunity.
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项目成果

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Amariliz Rivera其他文献

Amariliz Rivera的其他文献

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{{ truncateString('Amariliz Rivera', 18)}}的其他基金

Mechanisms of vaccine protection against AIDS-associated Cryptococcus infection
疫苗预防艾滋病相关隐球菌感染的机制
  • 批准号:
    10574561
  • 财政年份:
    2019
  • 资助金额:
    $ 63.08万
  • 项目类别:
Mechanisms of vaccine protection against AIDS-associated Cryptococcus infection
疫苗预防艾滋病相关隐球菌感染的机制
  • 批准号:
    10793773
  • 财政年份:
    2019
  • 资助金额:
    $ 63.08万
  • 项目类别:
Mechanisms of vaccine protection against AIDS-associated Cryptococcus infection
疫苗预防艾滋病相关隐球菌感染的机制
  • 批准号:
    10542652
  • 财政年份:
    2019
  • 资助金额:
    $ 63.08万
  • 项目类别:
Mechanisms of vaccine protection against AIDS-associated Cryptococcus infection
疫苗预防艾滋病相关隐球菌感染的机制
  • 批准号:
    10097978
  • 财政年份:
    2019
  • 资助金额:
    $ 63.08万
  • 项目类别:
Mechanisms of vaccine protection against AIDS-associated Cryptococcus infection
疫苗预防艾滋病相关隐球菌感染的机制
  • 批准号:
    10335166
  • 财政年份:
    2019
  • 资助金额:
    $ 63.08万
  • 项目类别:
Mechanisms of vaccine protection against AIDS-associated Cryptococcus infection
疫苗预防艾滋病相关隐球菌感染的机制
  • 批准号:
    9886185
  • 财政年份:
    2019
  • 资助金额:
    $ 63.08万
  • 项目类别:
Mechanisms of vaccine protection against AIDS-associated Cryptococcus infection
疫苗预防艾滋病相关隐球菌感染的机制
  • 批准号:
    10274411
  • 财政年份:
    2019
  • 资助金额:
    $ 63.08万
  • 项目类别:
Regulation of antifungal immunity by monocyte-derived dendritic cells
单核细胞来源的树突状细胞抗真菌免疫的调节
  • 批准号:
    9263884
  • 财政年份:
    2015
  • 资助金额:
    $ 63.08万
  • 项目类别:
Role of CCR2+ monocytes and Mo-DCs in defense against IA and GVHD development
CCR2 单核细胞和 Mo-DC 在防御 IA 和 GVHD 发展中的作用
  • 批准号:
    8701013
  • 财政年份:
    2013
  • 资助金额:
    $ 63.08万
  • 项目类别:
Role of CCR2+ monocytes and Mo-DCs in defense against IA and GVHD development
CCR2 单核细胞和 Mo-DC 在防御 IA 和 GVHD 发展中的作用
  • 批准号:
    8637016
  • 财政年份:
    2013
  • 资助金额:
    $ 63.08万
  • 项目类别:

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