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• W2531769105 abstract "Staphylococcus aureus is a leading cause of community- and nosocomial-acquired infections, with a propensity for biofilm formation. S. aureus biofilms actively skew the host immune response toward an anti-inflammatory state; however, the biofilm effector molecules and the mechanism(s) of action responsible for this phenomenon remain to be fully defined. The essential bacterial second messenger cyclic diadenylate monophosphate (c-di-AMP) is an emerging pathogen-associated molecular pattern during intracellular bacterial infections, as c-di-AMP secretion into the infected host cytosol induces a robust type I interferon (IFN) response. Type I IFNs have the potential to exacerbate infectious outcomes by promoting anti-inflammatory effects; however, the type I IFN response to S. aureus biofilms is unknown. Additionally, while several intracellular proteins function as c-di-AMP receptors in S. aureus, it has yet to be determined if any extracellular role for c-di-AMP exists and its release during biofilm formation has not yet been demonstrated. This study examined the possibility that c-di-AMP released during S. aureus biofilm growth polarizes macrophages toward an anti-inflammatory phenotype via type I interferon signaling. DacA, the enzyme responsible for c-di-AMP synthesis in S. aureus, was highly expressed during biofilm growth, and 30 to 50% of total c-di-AMP produced from S. aureus biofilm was released extracellularly due to autolytic activity. S. aureus biofilm c-di-AMP release induced macrophage type I IFN expression via a STING-dependent pathway and promoted S. aureus intracellular survival in macrophages. These findings identify c-di-AMP as another mechanism for how S. aureus biofilms promote macrophage anti-inflammatory activity, which likely contributes to biofilm persistence." @default.
• W2531769105 created "2016-10-21" @default.
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• W2531769105 creator A5091655483 @default.
• W2531769105 date "2016-12-01" @default.
• W2531769105 modified "2023-10-16" @default.
• W2531769105 title "Cyclic di-AMP Released from Staphylococcus aureus Biofilm Induces a Macrophage Type I Interferon Response" @default.
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• W2531769105 doi "https://doi.org/10.1128/iai.00447-16" @default.
• W2531769105 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5116733" @default.
• W2531769105 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27736778" @default.
• W2531769105 hasPublicationYear "2016" @default.
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