心磷脂
促炎细胞因子
脂多糖
先天免疫系统
细胞生物学
生物
免疫系统
细胞因子
线粒体
金黄色葡萄球菌
线粒体内膜
炎症
巨噬细胞
微生物学
免疫学
生物化学
细菌
膜
磷脂
体外
遗传学
作者
Mack B. Reynolds,Basel H. Abuaita,Mary O’Riordan
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2020-05-01
卷期号:204 (1_Supplement): 152.14-152.14
被引量:1
标识
DOI:10.4049/jimmunol.204.supp.152.14
摘要
Abstract During the immune response, mitochondria serve as a hub for innate immune signaling molecules, such as mitochondrial antiviral signaling protein (MAVS) and Nod Like Receptor Family Pyrin Domain Containing 3 (NLRP3). Cardiolipin, a class of phospholipids found primarily in the inner mitochondrial membrane (IMM), regulates mitochondrial function and cellular stress. In lipopolysaccharide (LPS)-stimulated macrophages, CL translocates from the IMM to the outer mitochondrial membrane (OMM) and recruits NLRP3 to promote inflammasome activation. However, the role of CL in macrophage antibacterial responses remains ill defined. Here, we have made CL-deficient RAW264.7 (RAW) cells by stably knocking down Cardiolipin Synthase (Crls1). Upon infection with methicillin-resistant Staphylococcus aureus (MRSA), Crls1 KD RAW cells showed markedly decreased expression and production of cytokines IL-6, IL-1β, and IFN-β compared to control cells, while TNF-α levels remained similar. For IL-6 and IFN-β, transcript and protein levels in Crls1 KD RAW cells were comparable to unstimulated controls. Surprisingly, these cells showed normal MRSA killing and NF-kB p65 nuclear translocation. These findings suggest a novel role for CL in transcript-level regulation of cytokines during infection. To further investigate CL-dependent innate immune functions, we will use RAW cells expressing a GFP-tagged CL-binding protein, Stomatin-like Protein-2-GFP, to track CL dynamics at membrane-level resolution using 3D structured illumination microscopy. This approach supports earlier studies that describe increased CL OMM localization in response to LPS. Our data suggest an underappreciated role for CL in macrophage responses to MRSA infection.
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