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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,8,2]]},"abstract":"<jats:p>\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    is an opportunistic pathogen and chief among bloodstream-infecting bacteria.\n                    <jats:italic>S. aureus<\/jats:italic>\n                    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\n                    <jats:italic>S. aureus<\/jats:italic>\n                    using RNA-sequencing (RNA-Seq). We found that the overall transcriptional response to\n                    <jats:italic>S. aureus<\/jats:italic>\n                    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\n                    <jats:italic>S. aureus<\/jats:italic>\n                    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\n                    <jats:italic>S. aureus<\/jats:italic>\n                    clones but absent in blood exposed to heat-killed\n                    <jats:italic>S. aureus<\/jats:italic>\n                    or blood infected with the less virulent staphylococcal species\n                    <jats:italic>Staphylococcus epidermidis<\/jats:italic>\n                    . Notably, this signature was also present in patients with\n                    <jats:italic>S. aureus<\/jats:italic>\n                    bacteremia. We identified the master regulator\n                    <jats:italic>S. aureus<\/jats:italic>\n                    exoprotein expression (SaeRS) and the SaeRS-regulated pore-forming toxins as key mediators of the transcriptional suppression. The\n                    <jats:italic>S. aureus<\/jats:italic>\n                    \u2013mediated suppression of chemokine and cytokine transcription was reflected by circulating protein levels in the plasma. Wild-type\n                    <jats:italic>S. aureus<\/jats:italic>\n                    elicited a soluble milieu that was restrictive in the recruitment of human neutrophils compared with strains lacking\n                    <jats:italic>saeRS<\/jats:italic>\n                    . Thus,\n                    <jats:italic>S. aureus<\/jats:italic>\n                    blunts the inflammatory response resulting in impaired neutrophil recruitment, which could promote the survival of the pathogen during invasive infection.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2123017119","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T14:37:08Z","timestamp":1658846228000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":30,"title":["<i>Staphylococcus aureus<\/i>\n                    induces a muted host response in human blood that blunts the recruitment of neutrophils"],"prefix":"10.1073","volume":"119","author":[{"given":"Erin E.","family":"Zwack","sequence":"first","affiliation":[{"name":"Department of Microbiology, New York University Grossman School of Medicine, New York, NY 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