The Salmonella pathogenicity island 1 injectisome reprograms host cell translation to evade the inflammatory response.

During bacterial infection both the host cell and its invader must rapidly divert resources to synthesize specific proteins. For the host, these factors may be needed for innate immune responses, including programmed cell death, and in the bacteria newly synthesized proteins may include survival factors that counteract host defences. Salmonella is an important bacterial pathogen that invades and multiplies within host cells. It is well established that epithelial cell invasion is dependent upon the Salmonella pathogenicity island 1 (SPI-1) type III injectisome, a biological needle that penetrates host cells and injects effectors that promote bacterial internalization. However, the importance of the SPI-1 injectisome in infection of professional phagocytes such as macrophages, the predominant host cell type supporting systemic infection, is less clear. Through time-resolved parallel transcriptomic and translatomic studies of macrophage infection, we reveal SPI-1 injectisome-dependent infection of macrophages triggers rapid translation of transcription factors, including Early Growth Response 1 (EGR1). Despite EGR1's short half-life, its swift synthesis, driven by untranslated regions of its mRNA, is sufficient to inhibit the transcription of pro-inflammatory genes; this restrains inflammation and macrophage death which would otherwise abort systemic infection. This demonstrates the importance of translational activation in host-pathogen dynamics during bacterial infection.