Unknown

Dataset Information

0

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


ABSTRACT: Staphylococcus aureus is an opportunistic pathogen and chief among bloodstream-infecting bacteria. S. aureus 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 S. aureus using RNA-sequencing (RNA-Seq). We found that the overall transcriptional response to S. aureus 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 S. aureus 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 S. aureus clones but absent in blood exposed to heat-killed S. aureus or blood infected with the less virulent staphylococcal species Staphylococcus epidermidis. Notably, this signature was also present in patients with S. aureus bacteremia. We identified the master regulator S. aureus exoprotein expression (SaeRS) and the SaeRS-regulated pore-forming toxins as key mediators of the transcriptional suppression. The S. aureus-mediated suppression of chemokine and cytokine transcription was reflected by circulating protein levels in the plasma. Wild-type S. aureus elicited a soluble milieu that was restrictive in the recruitment of human neutrophils compared with strains lacking saeRS. Thus, S. aureus blunts the inflammatory response resulting in impaired neutrophil recruitment, which could promote the survival of the pathogen during invasive infection.

SUBMITTER: Zwack EE 

PROVIDER: S-EPMC9351360 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

<i>Staphylococcus aureus</i> induces a muted host response in human blood that blunts the recruitment of neutrophils.

Zwack Erin E EE   Chen Ze Z   Devlin Joseph C JC   Li Zhi Z   Zheng Xuhui X   Weinstock Ada A   Lacey Keenan A KA   Fisher Edward A EA   Fenyö David D   Ruggles Kelly V KV   Loke P'ng P   Torres Victor J VJ  

Proceedings of the National Academy of Sciences of the United States of America 20220726 31


<i>Staphylococcus aureus</i> is an opportunistic pathogen and chief among bloodstream-infecting bacteria. <i>S. aureus</i> 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 <i>S. aureus</i> using RNA-sequencing (RNA-Seq). We found that the overall transcriptional response to <i>S. aureus</i> was weak both in the number of genes and in the magnitude of response. Using  ...[more]

Similar Datasets

2022-07-20 | GSE193219 | GEO
| PRJNA795455 | ENA
| S-EPMC6738831 | biostudies-literature
| S-EPMC6531466 | biostudies-literature
| S-EPMC4011196 | biostudies-literature
| S-EPMC11323798 | biostudies-literature
2012-05-21 | GSE38053 | GEO
| S-EPMC4401519 | biostudies-literature
| S-EPMC3418743 | biostudies-literature
| S-EPMC7966777 | biostudies-literature