Staphylococcus aureus second immunoglobulin-binding protein (Sbi) is a unique type 2-promoting virulence factor that induces IL-33 and thymic stromal lymphopoietin (TSLP) release. This mechanism is essential for the development of S. aureus-induced eczema in the widely used NC/Tnd mouse model of human atopic dermatitis (AD). Microbiome shifts in AD suggest that microbiota could modulate the disease. We therefore sought to identify skin bacteria that attenuate S. aureus-induced IL-33/TSLP release from keratinocytes. Micrococcus luteus was unique among skin isolates in its ability to negate cytokine induction. The bioactive factor responsible was identified using fractionation, LC-MS and recombinant proteins, as the serine protease "PA domain protein" (PADP). Immunoblotting and ELISA confirmed Sbi and IL-33 degradation by PADP. This was not observed with the M. luteus type strain which contains a frame shift mutation within the PADP active site. These data provide new insights into the role of skin microbiota in AD and highlights their potential as topical therapeutics.
Elias et al. (Wed,) studied this question.