Will It Be Possible in the Future to Target Innate Immunity Against Staphylococcus aureus Using Resident Microbiota and Plant Extracts?

Staphylococcus aureus remains a major cause of hospital- and community-acquired infections, successfully evading host defense mechanisms and escaping proposed vaccination strategies. The effective response of professional phagocytes is crucial in limiting the spread, tissue invasion, and subsequent infection by S. aureus. However, direct stimulation of innate immunity with S. aureus antigens is too risky due to their strong proinflammatory properties. Therefore, this study aimed to test the hypothesis that plant extracts trigger the gentle release of staphylococcal bioactive components that can modulate innate immunity. This strategy was tested in vitro; however, it may have future applications by employing the resident microbiota and dietary supplements containing plant extracts. In this study, the THP-1-derived macrophages were exposed to the supernatants of planktonic and biofilm S. aureus cultures pretreated with Viburnum opulus L. bark and fruit extracts. Vancomycin (VAN) and chlorogenic acid (ChA), used at subinhibitory concentrations, were included for comparison regarding the release of S. aureus active components. The cells were also exposed to purified bacterial cell wall components. Various elements of the immune response were assessed, including surface expression of cluster of differentiation (CD11c, CD206) via flow cytometry, cytokine production (tumor necrosis factor-alpha [TNF-α] and interleukin 10 [IL-10]) via ELISA, and S. aureus phagocytosis and intracellular killing using fluorescein isothiocyanate (FITC)-labeled bacteria and Alamar Blue staining. It was demonstrated that both supernatants from planktonic and biofilm S. aureus cultures pre-exposed to V. opulus extracts, as well as the bacterial cell wall components themselves, significantly increased TNF-α and IL-10 production by THP-1-derived macrophages and visibly reduced intracellular multiplication of engulfed S. aureus. The lack of changes in the surface CD marker expression may be a limitation of the model used (phorbol-12-myristate-13-acetate [PMA]-differentiated THP-1) rather than the phenomenon itself, that leads to a "ceiling effect". To sum up, the study presents V. opulus extracts as the triggers to release bioactive components from S. aureus cells, able to target innate immunity against staphylococci, which may be used in the future.