Toll-like receptor 4-driven translational reprogramming in macrophages is unaffected by Salmonella SPI-1 activity

Changes in gene expression during bacterial infection are the combined result of altered transcription and translation, with the latter comparatively understudied. Gram-negative bacteria rapidly trigger cytokine gene transcription in macrophages through the activation of pathogen-associated molecular pattern receptors, for example the detection of Salmonella lipopolysaccharide (LPS) from the bacterial cell envelope by Toll-like receptor 4 (TLR4). Here, through time-resolved parallel translatomic and transcriptomic profiling, we now show temporal TLR4-specific translational upregulation of cell signaling proteins in macrophages induced by Salmonella . While transcriptional upregulation of these genes is dampened through the activity of the Salmonella SPI-1 type 3 secretion system, a robust translational response remains. These data reveal an important host-pathogen translational regulatory network that modifies the innate immune response of macrophages to infection.