O05 Distinct epidermal cell populations and single-cell gene expression signatures are associated with Staphylococcus aureus in atopic dermatitis

Abstract Introduction and aims Atopic dermatitis (AD) affects 15–30% of children and 5–8% of adults and carries profound functional, psychological and social morbidity. Staphylococcus aureus is increased in AD and correlates with disease severity. However, the crosstalk between the host immune system and S. aureus remains poorly understood. The aim of this project was to compare the skin microbiome and single-cell transcriptome in order to examine interactions between S. aureus and cutaneous immune responses in AD. Methods Skin microbiome swabs and underlying skin biopsies were obtained from lesional and nonlesional skin of adults with AD (n = 4 participants, n = 8 biopsy and swab samples). S. aureus relative abundance was quantified using shotgun metagenomic sequencing. The host single-cell gene expression profile was quantified through single-cell RNA sequencing of the skin biopsies. Results Epidermis cellular proportions are different between SA-high AD (lesional and nonlesional samples with S. aureus relative abundance > 35%) and SA-low AD (lesional and nonlesional samples with S. aureus relative abundance < 10%), with increased T cells, macrophages and dendritic cells seen in SA-high AD. The increased T cells express the proinflammatory cytokine genes IL13, IL22 and IL26 in SA-high AD. There are also increased macrophages and dendritic cells expressing the T helper 2 chemokine gene CCL17 (TARC). In SA-high AD there are more undifferentiated keratinocytes, basal keratinocytes and keratinocytes expressing skin barrier impairment markers galectin-7 and suprabasin. In SA-low AD keratinocytes expressing the hair follicle stem cell marker keratin 15 and the skin barrier gene ZFP36 are increased. Conclusions These findings show distinct cell populations and cell-specific cutaneous gene expression signatures associated with S. aureus in both lesional and nonlesional AD. In SA-high AD there are increased immune cells expressing proinflammatory cytokine genes, as well as increased keratinocytes expressing skin barrier impairment markers. These findings suggest novel mechanisms which may underlie S. aureus–host interactions in AD and might be targeted therapeutically.