TRR Skin Immunity

How skin inflammation is shaped by interaction of Staphylococcus aureus with skin cells and skin microbiota

01.07.2015 bis 30.06.2019

While healthy human skin is hardly colonized by Staphylococcus aureus these bacteria are frequently found on the skin of atopic dermatitis patients and are thought to contribute actively to skin inflammation and eczema formation. However, it has remained unknown how immune-modulatory S. aureus molecules affect skin cell functions and S. aureus capacities to thrive on skin. Moreover, how S. aureus interacts with the skin microbiota to compete for nutrients and shape skin inflammation remains elusive. Our groups have collaboratively identified and characterized bacterial or host factors governing S. aureus colonization and immune-modulation such as staphylococcal adhesins and microbe-associated molecular patterns (MAMPs) or new human skin antimicrobial peptides (dermcidin) and MAMP receptors (FPR2). Based on evidence from our and other groups we will analyse if and how S. aureus requires and actively adjusts a favourable level of inflammation on the skin. Moreover, we will study how S. aureus interacts with skin microbiota via bacteriocins and metabolic competition or via modulation of skin cells as a prerequisite for skin colonization. Using our collections of defined S. aureus mutants, immune-modulatory molecules, and colonization models we will study the following aspects: The impact of S. aureus immunomodulatory factors such as lipopeptides, formylated peptides, or phenol-soluble modulins (PSMs) and cognate skin receptors on bacterial colonization will be explored in vitro with cultivated keratinocytes and in vivo in our established skin infection model. The inhibitory and metabolic interference of S. aureus with skin microbiota along with capacities of skin commensals to interfere with S. aureus colonization will be analyzed by investigating the capacity of skin bacteria to produce bacteriocins or to withdraw essential nutrients. Our project should help to better understand skin inflammation with the ultimate goal to find new ways for treating bacteria-associated skin disorders.