Intracellular persistence of Staphylococcus aureus in peripheral immune cells

S. aureus is a causative agent for many diseases, including sepsis. There is increasing evidence that S. aureus is able to persist intracellularly in immune cells leading to chronic,infections. Thus, peripheral immune cells could act as ‘Trojan horses’, offering S. aureus protection. Further, there is evidence that a phenotype switch to SCVs promotes intracellular persistence. The focus of this study was to characterise the potential of peripheral immune cells as a putative niche for S. aureus persistence. Therefore, the interaction of S. aureus with PMN and monocytes isolated from human donors was systematically investigated The influence of the agr of S. aureus, which controls the main virulence factors, was tested using an S. aureus agr knock-out strain as a surrogate for SCVs. The results reveal that S. aureus was capable of infecting peripheral immune cells. Initially, the bacteria were equally internalised by monocytes and PMN in the early phase of infection. Bacterial clearance differed between wildtype and agr k.o. strain with the agr mutant being less efficiently cleared by both professional phagocytes. Moreover, S. aureus was able to persist in peripheral immune cells for up to 24 h p.i. During bacterial persistence, the agr mutant strain had significant advantages to survive demonstrated by a higher bacterial burden within both immune cell types. Monocytes were characterised as the preferred bacterial persistence niche of both immune cell types. In both immune cell types, agr deficient S. aureus generated a lower ROS signal compared to wildtype infected immune cells during the pathogen’s establishment of persistence. This supports the observed reduced immune clearance of intracellular agr deficient bacteria. Overall, entering a dormant state by downregulation of the agr operon represents a potential advantage for the pathogen to disseminate via high-jacking peripheral immune cells as potential vectors of transmission.