In particular, we show that Terc−/− macrophages adopt senescence‐like phenotype and induce mitochondrial distress facilitating mtDNA leakage, which in turn triggers the cGAS/STING pathways and NLRP3 inflammasome activation, and thereby predisposes Terc−/− mice severe disease during normally non‐lethal infection. Here, TERC is linked to infection.