Molecular mechanisms of phagocytosis and immune activation by TREM receptors
TREM受体吞噬和免疫激活的分子机制
基本信息
- 批准号:RGPIN-2020-04032
- 负责人:
- 金额:$ 2.99万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2020
- 资助国家:加拿大
- 起止时间:2020-01-01 至 2021-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Macrophages, along with other phagocytes, have the inherent ability to engulf or “eat” foreign material, in a process termed phagocytosis. Phagocytosis is a highly complex process that involves a myriad of signaling events that ultimately results in the engulfment of microbial pathogens, or the clearance of dying cells and debris within multicellular organisms. As such, phagocytosis plays a key role in both cellular immunity and tissue homeostasis. Macrophages can recognize and distinguish specific particles due the presence of a variety of cell surface receptors that can initiate the phagocytosis process. The identification and characterization of such receptors remains critical for a comprehensive understanding of phagocytosis. Since their discovery almost 20 years ago, multiple studies have demonstrated that the Triggering Receptor Expressed on Myeloid cells (TREM) family of receptors play an important role in regulating inflammation. In particular, TREM1 and TREM2 have been well characterized in immune regulation and neurodegenerative diseases, but their role in phagocytosis remains unclear. There are conflicting reports on whether TREM2 functions to phagocytose bacteria. As such, there remains a major knowledge gap in whether and how TREM2 controls phagocytosis.
We have recently discovered that TREM2 can directly bind to Mycobacterium tuberculosis (Mtb), the pathogenic bacteria responsible for tuberculosis. Preliminary studies also show that genetic deletion of TREM2 in macrophages dramatically impairs their ability to phagocytose Mtb. We therefore hypothesize that TREM2 can recognize and facilitate the uptake of mycobacteria, which can then impact the differential activation of antibacterial and inflammatory responses. To address this knowledge gap, we aim to: (1) identify the bacterial ligand recognized by TREM2, (2) examine the spatial-temporal regulation of TREM2 in response to bacterial stimuli as a means to elucidate the intracellular signaling pathways mediated through ligation of TREM2, and (3) determine the immunological effects of TREM2-mediated phagocytosis, including the activation of antimicrobial pathways, cytokine production, and ultimately bacterial survival. The long-term goal of this research program is to understand the molecular basis of how TREM-like receptors, many of which are uncharacterized, controls phagocytosis in all myeloid cell types. Given that phagocytic receptors are essential for host defense, nutrient acquisition, inflammation, and tissue homeostasis, the advancement of knowledge on these receptors will contribute answers to many important biological questions relevant for all organisms.
巨噬细胞和其他吞噬细胞一样,具有吞噬外来物质的固有能力,这一过程被称为吞噬作用。吞噬作用是一个高度复杂的过程,涉及无数的信号事件,最终导致微生物病原体的吞噬,或多细胞生物中死亡细胞和碎片的清除。因此,吞噬作用在细胞免疫和组织稳态中都起着关键作用。巨噬细胞能够识别和区分特定的颗粒是由于多种细胞表面受体的存在,这些受体可以启动吞噬过程。这些受体的鉴定和表征对于全面了解吞噬作用仍然至关重要。自近20年前发现以来,多项研究表明,骨髓细胞触发受体(TREM)受体家族在调节炎症中起着重要作用。特别是TREM1和TREM2已经在免疫调节和神经退行性疾病中得到了很好的表征,但它们在吞噬作用中的作用尚不清楚。关于TREM2是否具有吞噬细菌的功能,目前的报道相互矛盾。因此,TREM2是否以及如何控制吞噬仍然存在很大的知识空白。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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Sun, JimJian其他文献
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{{ truncateString('Sun, JimJian', 18)}}的其他基金
Molecular mechanisms of phagocytosis and immune activation by TREM receptors
TREM受体吞噬和免疫激活的分子机制
- 批准号:
RGPIN-2020-04032 - 财政年份:2022
- 资助金额:
$ 2.99万 - 项目类别:
Discovery Grants Program - Individual
Molecular mechanisms of phagocytosis and immune activation by TREM receptors
TREM受体吞噬和免疫激活的分子机制
- 批准号:
RGPIN-2020-04032 - 财政年份:2021
- 资助金额:
$ 2.99万 - 项目类别:
Discovery Grants Program - Individual
Molecular mechanisms of phagocytosis and immune activation by TREM receptors
TREM受体吞噬和免疫激活的分子机制
- 批准号:
DGECR-2020-00006 - 财政年份:2020
- 资助金额:
$ 2.99万 - 项目类别:
Discovery Launch Supplement
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