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Quorum sensing by Streptococcus pyogenes induces global inflammatory suppression in host macrophages

ABSTRACT: Streptococcus pyogenes, or Group A Strep (GAS), a significant human pathogen, employs quorum sensing (QS) systems to coordinate its behavior and genetic regulation in order to enhance survival. Our previous research established that one such QS system, the Rgg2/3 system, has the ability to suppress macrophage NFkB activity and production of pro-inflammatory cytokines. Yet, the scope of suppression was undetermined, and the mechanism remained elusive. In this study, we used transcriptomic and phosphoproteomic approaches to elucidate the extent and mechanisms of QS-mediated immune suppression. We found QS-ON GAS broadly suppressed most inflammatory transcriptional pathways including those of NFkB, type I and type II interferon responses, and intracellular stress responses. Yet, we found no alternative transcriptional programs being activated instead. Additionally, phosphoproteomics showed no disruption upstream in typical inflammatory pathways such as those related to NFkB and MAPK activation, which we successfully confirmed. Instead, the proteomic data highlighted a potential role for epigenetic mechanisms of inflammatory regulation. Despite this, measuring DNA methylation and inhibiting important histone and chromatin modifiers did not reveal which if any epigenetic regulation protein might be involved in the mechanisms of suppression. Still, these findings expand our understanding of QS-mediated suppression and of GAS virulence strategies that appear to target irregular means of restricting inflammation. Uncovering this mechanism will offer invaluable insight into GAS, itself, as well as understudied immunological pathways.

ORGANISM(S): Mus musculus

PROVIDER: GSE289076 | GEO | 2025/02/08

REPOSITORIES: GEO

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