3D model of human epidermis exposed to Staphylococci reveals keratinocyte responses unique to atopy-associated S. aureus challenge.
The interplay between microbiota and skin cells is a key factor underlying the pathophysiology of this barrier organ. Keratinocytes, the main components of the epidermis, are crucial for skin barrier function, but their responses to different bacteria are not well understood. We present a high-throughput analysis of the transcriptome of human epidermal-like organoids exposed to two vastly different bacterial skin colonists: Staphylococcus epidermidis and Staphylococcus aureus, which are commonly associated with mostly positive and negative interactions with the host, respectively. We observed partly overlapping but predominantly divergent epidermal changes in response to both bacteria. Among the genes most affected by S. aureus, those related to lipid metabolism were predominant. This work was supported by grants from the Polish National Science Center (UMO-2014/12/W/NZ6/00454 and 2019/35/B/NZ6/03357) and by a grant for research projects for Young Scientists and PhD students from the Jagiellonian University (N19/MNS/000020). The open-access publication has been supported by the Faculty of Biochemistry, Biophysics and Biotechnology under the Strategic Programme Excellence Initiative at Jagiellonian University in Krakow, Poland. Overall design: Generated 3D organotypic cultures of human keratinocytes from 3 separate healthy donors were exposed to microbial challange from either live Staphylococcus aureus or Staphylococcus epidermidis bacterial cells, with sterlie PBS as a control. After 24h, RNA was isolated and RNAseq analysis was perfomed studying the differences in expression pattern between tested conditions.