Salmonella impairs macrophage immunity through effector-independent rapid translational induction in response to membrane puncture by the SPI-1 injectisome

Salmonella is a globally important pathogen that actively invades and replicates within host cells, including epithelial cells and macrophages, during infection. Bacterial internalization is predominantly orchestrated by the Salmonella SPI-1 Type III secretion system (T3SS). The SPI-1 T3SS transports effectors directly through the host cell membrane and into its cytosol to trigger Salmonella uptake. Here, we demonstrate that Salmonella rapidly synthesizes SPI-1 components as they encounter potential host macrophages, priming the bacteria for host invasion. Assembly of the T3SS in the host membrane results in transient pore formation. We show that this leads to the surge of translational induction of host transcription factors, including Egr1 . In macrophages, the rapid synthesis of EGR1 results in the suppression of immune response and pro-apoptotic genes. Thus, SPI-1-mediated membrane damage limits the macrophage immune response to Salmonella infection ### Competing Interest Statement The authors have declared no competing interest.