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- W4313369044 abstract "Abstract Group A Streptococcus (GAS) employs numerous systems to regulate genetic programs, and infection causes a spectrum of outcomes in humans ranging from commensalism to superficial disease (e.g. pharyngitis) or invasive disease (e.g. necrotizing fasciitis). Quorum sensing (QS) is a mechanism of cell-to-cell communication used by bacteria to synchronize genetic programs across populations. We previously determined that activation of the Rgg2/3 QS system in GAS results in bacterial surface alterations, leading us to hypothesize that QS could alter interactions with host cells. To test this, macrophages were infected with mutant strains of GAS containing either constitutively activated (QS-ON) or repressed (QS-OFF) Rgg2/3, and pro-inflammatory cytokine responses were measured. Macrophage responses to QS-ON GAS were attenuated, resulting in decreased NFκB activity and decreased production of TNFα, IL-6, and IFNβ compared to infection with QS-OFF GAS. Macrophage responses to mixed QS populations remained attenuated, suggesting the effect of QS-ON GAS is dominant. Furthermore, QS-ON GAS suppressed TNFα responses induced by various TLR agonists, suggesting an active mechanism of repression occurs downstream in these pathways. Together, these data suggest that GAS utilizes Rgg2/3 QS to manipulate innate immune responses. Disabling bacterial communication using a QS-inhibitor restored pro-inflammatory responses against the bacteria, highlighting its potential application as an alternative treatment strategy." @default.
- W4313369044 created "2023-01-06" @default.
- W4313369044 creator A5059699591 @default.
- W4313369044 creator A5082921592 @default.
- W4313369044 date "2020-05-01" @default.
- W4313369044 modified "2023-09-27" @default.
- W4313369044 title "Innate immune responses are manipulated by a streptococcal communication system" @default.
- W4313369044 doi "https://doi.org/10.4049/jimmunol.204.supp.156.18" @default.
- W4313369044 hasPublicationYear "2020" @default.
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