巨内在的MDA5-IRF5轴驱动HIV-1内部含RNA诱导的炎症反应
Sita Ramaswamy1, Hisashi Akiyama1, Jacob Berrigan1
1Department of Virology, Immunology, and Microbiology, Boston University Chobanian and Avedisian School of Medicine, Boston, United States of America.
The Journal of clinical investigation
|June 10, 2025
概括
黑色素瘤分化相关蛋白5 (MDA5) 在巨细胞中感知HIV-1内部含RNA (icRNA),驱动I型干扰素反应. 这条涉及IRF5的途径有助于艾滋病毒感染的老年人慢性炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 尽管抗逆转录病毒疗法 (ART),但持续的HIV-1储存会导致免疫激活.
- 感染HIV-1的巨细胞通过不清楚的机制调解慢性先天免疫激活.
- 艾滋病毒-1内源含RNA (icRNA) 的细胞质表达激活了MAVS介导的I型干扰素 (IFN) 反应.
研究的目的:
- 阐明MDA5在感知HIV-1的icRNA和启动先天免疫反应中的作用.
- 研究包括IRF5在内的下游信号通路,涉及HIV-1 icRNA诱导的炎症.
- 为了探索与年龄相关的HIV-1 icRNA感应和促炎反应的差异.
主要方法:
- 巨细胞被用来研究HIV-1 icRNA感知途径.
- 调节了MDA5和RIG-I的表达和功能.
- 测量了干扰素 (IFN) 和IP-10的反应.
- 分析了来自年轻和年长个体的单细胞和巨细胞.
主要成果:
- MDA5,而不是RIG-I或内体TLRs,对于感知HIV-1的icRNA和诱导巨细胞中的I型IFN和IP-10至关重要.
- 在MDA5依赖的IP-10诱导过程中,需要激活IRF5.
- 来自老年人的巨体呈现出更高的构成性IRF5和增强的HIV-1 icRNA诱导的IP-10产生.
- 消去IRF5减弱了老年巨细胞中增强的炎症反应.
结论:
- MDA5是巨细胞中HIV-1 icRNA的关键传感器,启动MAVS依赖的I型IFN和IP-10反应.
- IRF5是MDA5介导的HIV-1 icRNA传感下游的促炎级联的关键调解者.
- MDA5-IRF5通路的失调可能会导致艾滋病毒感染的老年人慢性炎症.
相关概念视频
01:29Immune Response Against Viral Pathogens
760
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
760
01:24T Cell Types and Functions
959
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
959