induces a muted host response in human blood that blunts the recruitment of neutrophils.

is an opportunistic pathogen and chief among bloodstream-infecting bacteria. produces an array of human-specific virulence factors that may contribute to immune suppression. Here, we defined the response of primary human phagocytes following infection with using RNA-sequencing (RNA-Seq). We found that the overall transcriptional response to was weak both in the number of genes and in the magnitude of response. Using an ex vivo bacteremia model with fresh human blood, we uncovered that infection with resulted in the down-regulation of genes related to innate immune response and cytokine and chemokine signaling. This muted transcriptional response was conserved across diverse clones but absent in blood exposed to heat-killed or blood infected with the less virulent staphylococcal species . Notably, this signature was also present in patients with bacteremia. We identified the master regulator exoprotein expression (SaeRS) and the SaeRS-regulated pore-forming toxins as key mediators of the transcriptional suppression. The -mediated suppression of chemokine and cytokine transcription was reflected by circulating protein levels in the plasma. Wild-type elicited a soluble milieu that was restrictive in the recruitment of human neutrophils compared with strains lacking . Thus, blunts the inflammatory response resulting in impaired neutrophil recruitment, which could promote the survival of the pathogen during invasive infection.