Abstract
During the last few years, mitochondrial DNA has attained much attention as a modulator of immune responses. Due to common evolutionary origin, mitochondrial DNA shares various characteristic features with DNA of bacteria, as it consists of a remarkable number of unmethylated DNA as 2′-deoxyribose cytidine-phosphate-guanosine (CpG) islands. Due to this particular feature, mitochondrial DNA seems to be recognized as a pathogen-associated molecular pattern by the innate immune system. Under the normal physiological situation, mitochondrial DNA is enclosed in the double membrane structure of mitochondria. However, upon pathological conditions, it is usually released into the cytoplasm. Growing evidence suggests that this cytosolic mitochondrial DNA induces various innate immune signaling pathways involving NLRP3, toll-like receptor 9, and stimulator of interferon genes (STING) signaling, which participate in triggering downstream cascade and stimulating to produce effector molecules. Mitochondrial DNA is responsible for inflammatory diseases after stress and cellular damage. In addition, it is also involved in the anti-viral and anti-bacterial innate immunity. Thus, instead of entire mitochondrial importance in cellular metabolism and energy production, mitochondrial DNA seems to be essential in triggering innate anti-microbial immunity. Here, we describe existing knowledge on the involvement of mitochondrial DNA in the anti-microbial immunity by modulating the various immune signaling pathways.
Highlights
Mitochondria are subcellular organelles with highly dynamic properties and found in large numbers in all eukaryotic cells [1]
The escaped mitochondrial DNA following the microbial infection is detected by the cGAS/stimulator of interferon genes (STING) signaling pathway that causes TBK1/IRF3 dependent production of type I interferon and limits replication of microbes
Remarkable progress has been made in the last several years to describe the biological mechanisms by which the innate immune system recognizes microbial pathogens and integrates signals from pathogen associated molecular patterns to mount a precise immune response [158,159,160]
Summary
Mitochondria are subcellular organelles with highly dynamic properties and found in large numbers in all eukaryotic cells [1]. Mitochondria play a crucial biological role in cellular homeostasis They contain oxidative phosphorylation machinery that enables aerobic ATP production, and various metabolic pathways, including urea cycles, β-oxidation of fatty acids, and the tricarboxylic acid. Mitochondrial damage-associated molecular patterns and reactive oxygen species can activate anti-bacterial and anti-viral innate immune responses in mammals [1,4,5]. We describe the recent literature regarding the effect of microbial infection, viral and bacterial infection, on the release of mitochondrial DNA as well as its impact on the subsequent signaling pathways to limit the microbial infection. This article will help understand the relationship between microbial infection and mitochondrial DNA release and, subsequently, immune responses to limit infection
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