Figure 1: Interactions between Staphylococcus aureus, native skin commensals and host cells in healthy or diseased skin.
On healthy skin (left), commensals like coagulase-negativeStaphylococcus (CoNS) and the fungi Malassezia secrete a variety of compounds to inhibit the growth of the pathobiontStaphylococcus aureus (S. aureus ). CoNS secrete phenol soluble modulins (PSMs) and auto-inducing peptides, which inhibitS. aureus growth and virulence factor expression respectively. CoNS can stimulate host epidermal cells to produce anti-microbial peptides (AMPs) to further restrain S. aureus growth. Both CoNS and commensal Malassezia also secrete a variety of proteases, which disrupt S. aureus biofilm formation. These mechanisms contribute to T cell tolerance and likely optimize barrier function on healthy skin. On inflamed skin (right), increased S. aureuscolonization and biofilm formation can lead to heightened secretion of virulence factors such as PSMs, toxins and proteases that damage the stratum corneum. Host AMPs are present in lower amounts or are rendered less effective due to S. aureus activity and Th2 signalling.S. aureus can also suppress the growth or activity of skin commensals. Superantigens released by S. aureus can penetrate the epidermis and trigger dermal dendritic cells to drive T helper 2 (Th2) polarization and expansion. Excessive numbers of Th2 cells in turn, produce a variety of pro-inflammatory cytokines, which further exacerbate skin barrier dysfunction, IgE production by B-cells and mast cell degranulation. While the pre-flare skin (middle) is not inflamed, there might be decreases in the abundance of commensals which inhibitS. aureus , promoting its transition to a pathogenic state. These individuals have elevated Th2 responses and IgE compared to healthy skin, and are pre-disposed to severe itching in subsequent flares. (Created with BioRender.com)