Staphylococcus aureus induces miR-21 expression to promote bacterial persistence during nasal colonisation

Staphylococcus aureus nasal colonisation is commonplace among healthy individuals, yet the immune mechanisms enabling bacterial persistence remain unclear. S. aureus drives local immunosuppression during nasal colonisation to facilitate persistence. This study reveals that S. aureus subverts microRNA-21 activity to promote IL-10 production within nasal tissue, while simultaneously impeding local pro-inflammatory responses. MiR-21 activity helps establish a S. aureus-induced immunosuppressive microenvironment, which supports S. aureus persistence. Macrophages, which are key IL-10 producers, rapidly upregulate miR-21 upon S. aureus exposure. MiR-21 expression also coincides with an increase in intracellular survival of S. aureus within macrophages. Furthermore, S. aureus represses macrophage glycolysis to promote intracellular survival, which is dependent upon miR-21. Upon S. aureus colonisation, miR-21^-/- mice demonstrate an overall improved bacterial clearance compared to their wild-type counterparts. These findings highlight the targeting of miR-21, which controls glycolytic activity in macrophages, as a potential avenue to reducing bacterial persistence during S. aureus colonisation.