Microbes are recognized via the activation of multiple receptors and pathways with potentially overlapping, synergistic or oppositional effects. In PLoS Pathogens, Smale and colleagues assess the early transcriptional response of macrophages to Staphylococcus aureus to understand the contribution of and possible interactions between the TLR and STING pathways. Almost the entire early transcriptional response (<4 h) to live S. aureus is accounted for by these two pathways, with the remainder being driven by hypoxia-pathway signaling. However, TLR signaling is responsible for essentially the entire early transcriptional response to heat-killed bacteria. When assessed in isolation through the use of knockouts, the STING and TLR pathways trigger substantially overlapping transcriptional patterns, albeit with some differences in magnitude and kinetics. However, in an S. aureus skin-infection model, the STING and TLR pathways have opposing roles, with the former diminishing protection dependent on the cyokine IL-1.

PLoS Pathog. (13 Jul 2017) doi:10.1371/journal.ppat.1006496