Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen and University Medical Centre Groningen, Groningen, the Netherlands; Department of Obstetrics and Gynecology, University of Groningen and University Medical Centre Groningen, the Netherlands.
Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen and University Medical Centre Groningen, Groningen, the Netherlands.
Biochim Biophys Acta Mol Basis Dis. 2020 Oct 1;1866(10):165845. doi: 10.1016/j.bbadis.2020.165845. Epub 2020 May 28.
One of the main functions of mitochondria is production of ATP for cellular energy needs, however, it becomes more recognized that mitochondria are involved in differentiation and activation processes of immune cells. Upon activation, immune cells have a high need for energy. Immune cells have different strategies to generate this energy. In pro-inflammatory cells, such as activated monocytes and activated T and B cells, the energy is generated by increasing glycolysis, while in regulatory cells, such as regulatory T cells or M2 macrophages, energy is generated by increasing mitochondrial function and beta-oxidation. Except for being important for energy supply during activation, mitochondria also induce immune responses. During an infection, they release mitochondrial danger associated molecules (DAMPs) that resemble structures of bacterial derived pathogen associated molecular patterns (PAMPs). Such mitochondrial DAMPS are for instance mitochondrial DNA with hypomethylated CpG motifs or a specific lipid that is only present in prokaryotic bacteria and mitochondria, i.e. cardiolipin. Via release of such DAMPs, mitochondria guide the immune response towards an inflammatory response against pathogens. This is an important mechanism in early detection of an infection and in stimulating and sustaining immune responses to fight infections. However, mitochondrial DAMPs may also have a negative impact. If mitochondrial DAMPs are released by damaged cells, without the presence of an infection, such as after a trauma, mitochondrial DAMPs may induce an undesired inflammatory response, resulting in tissue damage and organ dysfunction. Thus, immune cells have developed mechanisms to prevent such undesired immune activation by mitochondrial components. In the present narrative review, we will describe the current view of mitochondria in regulation of immune responses. We will also discuss the current knowledge on disturbed mitochondrial function in immune cells in various immunological diseases.
线粒体的主要功能之一是为细胞能量需求产生 ATP，然而，人们越来越认识到线粒体参与免疫细胞的分化和激活过程。在激活后，免疫细胞对能量的需求很高。免疫细胞有不同的策略来产生这种能量。在促炎细胞中，如激活的单核细胞和激活的 T 和 B 细胞，能量是通过增加糖酵解产生的，而在调节细胞中，如调节性 T 细胞或 M2 巨噬细胞，能量是通过增加线粒体功能和β-氧化产生的。除了在激活过程中为能量供应提供重要作用外，线粒体还会诱导免疫反应。在感染过程中，它们会释放类似于细菌来源的病原体相关分子模式（PAMPs）结构的线粒体危险相关分子（DAMPs）。例如，带有低甲基化 CpG 基序的线粒体 DNA 或仅存在于原核生物和线粒体中的特定脂质，即心磷脂。通过释放这种 DAMPs，线粒体引导免疫反应朝向针对病原体的炎症反应。这是早期检测感染和刺激并维持免疫反应以抵抗感染的重要机制。然而，线粒体 DAMPs 也可能产生负面影响。如果没有感染的情况下，受损细胞释放线粒体 DAMPs，例如在创伤后，线粒体 DAMPs 可能会引发不必要的炎症反应，导致组织损伤和器官功能障碍。因此，免疫细胞已经开发出防止线粒体成分引起这种不必要免疫激活的机制。在本叙述性综述中，我们将描述线粒体在调节免疫反应中的当前观点。我们还将讨论各种免疫疾病中免疫细胞中线粒体功能障碍的最新知识。
