GSE174124
Tetracycline-induced mitohormesis mediates disease tolerance against influenza
Mitohormesis defines the increase in fitness mediated by adaptive responses to a mild mitochondrial stress. Tetracyclines inhibit not only bacterial but also mitochondrial translation, thus imposing a low level of mitochondrial stress to eukaryotic cells. We show here that the mitochondrial stress response induced by 2 tetracyclins (Tet1, Tet2)  improves survival and disease tolerance against lethal influenza virus (IFV) infection. Tolerance to IFV infection is associated with the induction of genes involved in lung epithelial cell and cilia function and with the down-regulation of inflammatory and immune related gene sets in the lung, liver, and kidney. Overall design: Design: We subjected 8 week-old female BALB/cN mice to either mock  or intranasal inoculation with 175 PFU of the IFV H1N1 PR8 strain (3 groups). The 3 infected groups were given vehicle, Tet1 (at 40 mpkd) or Tet2 (at 1 mpkd) by daily intraperitoneal injection (mock group respectively injected with vehicule as well). At day 7 post-inoculation, 5-6 mice were sacrified for organ collection.