Staphylococcus aureus-specific skin resident memory T cells protect against bacteria colonization but exacerbate atopic dermatitis-like flares in mice

Background The contribution of Staphylococcus aureus (S. aureus) to the exacerbation of atopic dermatitis (AD) is widely documented, but its role as a primary trigger of AD skin symptoms remains poorly explored. Objective To reappraise the main bacterial factors and underlying immune mechanisms by which S. aureus triggers AD-like inflammation. Methods We capitalized on a pre-clinical model, in which different clinical isolates were applied in the absence of any prior experimental skin injury. Results We report that the development of S. aureus-induced dermatitis depended on the nature of the S. aureus strain, its viability, the concentration of the applied bacterial suspension, the production of secreted and non-secreted factors, as well as the activation of accessory gene regulatory quorum sensing system. In addition, the rising dermatitis, which exhibited the well-documented AD cytokine signature, was significantly inhibited in inflammasome adaptor protein ASC- and monocyte/macrophage-deficient animals, but not in T- and B-cell-deficient mice, suggesting a major role for the innate response in the induction of skin inflammation. However, bacterial exposure generated a robust adaptive immune response against S. aureus, and an accumulation of S. aureus-specific γδ and CD4+ tissue resident memory T (Trm) cells at the site of previous dermatitis. The latter both contributed to worsen the flares of AD-like dermatitis upon new bacteria exposures, but also, protected the mice from persistent bacterial colonization. Conclusion These data highlight the induction of unique AD-like inflammation, with the generation of pro-inflammatory but protective Trm cells in a context of natural exposure to pathogenic S. aureus strains.