Staph-in-Skin · Deciphering the molecular mechanism of inflammation orchestrated by keratinocytes during Staphylococcus aureus infection in the skin

The skin provides a physical and immunological barrier to external environment and its homeostasis depends on interactions between keratinocytes, peripheral nerves, immune cells and microbiota. One of the bacteria that can colonise skin is Staphylococcus aureus and it can be part of healthy skin or pathogen causing skin infection. Importantly, in atopic dermatitis patients, which suffer from impaired skin barrier and microbiota dysbiosis, S. aureus is associated with severity of flares and exacerbation of inflammation. The inflammatory loop in the skin depends both on host and pathogen factors, but it is not fullyelucidated how this interaction is regulated.The proposed project will investigate novel mechanisms regulating the inflammation induced by S. aureus skin infection. The main focus will be on molecular mechanisms and regulation of pathogen sensing by keratinocytes. First, murine model of topical skin infection will be used to characterise how keratinocytes orchestrate immune response. Then, it will be examined in detail which S. aureus virulence factors induce inflammation in keratinocytes using different laboratory and clinical S. aureus strains. Finally, the role of characterised virulence factors and immunomodulators secreted by keratinocytes will be investigated in keratinocyte-immune cells interactions. To achieve the goals of this project, proteomics, next-generation sequencing, biochemistry, molecular biology and immunological assays will be applied.Overall, this project will contribute to greater understating of S. aureus-host immunity interactions with particular focus on regulation of keratinocyte inflammatory response. Moreover, identified novel signalling molecules in the skin and virulence factors of the pathogen can be explored in novel skin inflammation and infection treatments.