Neutrophils eradicate invading pathogens, but they can also cause substantial collateral damage to host tissues when inappropriately activated. However, whether or not the immune response of neutrophils is adjusted by a cell-intrinsic mechanism was not known. In her paper (https://www.ncbi.nlm.nih.gov/pubmed/30911105), Josi and colleagues could now show that the myeloid transcription factor PU.1 provides the transcriptional prerequisite for eradicating pathogens, but does also install a cell-intrinsic inhibitor program to safeguard the epigenome of neutrophils from undergoing uncontrolled activation.