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

Abstract

BackgroundThe 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. ObjectiveTo reappraise the main bacterial factors and underlying immune mechanisms by which S. aureus triggers AD-like inflammation. MethodsWe capitalized on a pre-clinical model, in which different clinical isolates were applied in the absence of any prior experimental skin injury. ResultsWe 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. ConclusionThese 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.