| Sumario: | The mitochondria play an important role in the activation of the innate immune system. This organelle modulates the metabolic reprogramming of the immune cell into proinflammatory or anti-inflammatory subtypes, which typically utilize very different metabolic pathways to fulfill their functions. It also acts as a signaling platform to activate immune routes in both immune and nonimmune cells, as it can generate agonists for inflammatory pathways, including toll-like receptors, inflammasomes, or the cyclic GMP–AMP synthase–stimulator of interferon genes pathway, which lead to the generation of proinflammatory cytokines and antiviral molecules such as type-I interferons. These novel functions of the mitochondria are important in the fight against pathogens, but also contribute to human disease when dysregulated. This review describes recent findings in this field and highlights the role of mitochondrial nucleic acids in the regulation of innate immune signaling pathways.
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