The dysregulation of host-microbe interactions has been associated with chronic inflammatory diseases such as atopic dermatitis (AD) and psoriasis. While the pathogenicity of skin microbiota members has been well-characterized, a growing body of evidence suggests that certain commensals possess beneficial properties for the host. To establish the feasibility of new biotherapeutic agent targeting skin inflammatory diseases, we identify that Staphylococcus cohnii is a skin commensal capable of inhibiting skin inflammation. Specifically, we used Tmem79 knockout mice which, under specific pathogen-free conditions, develop spontaneous dermatitis accompanied by an increase in both Staphylococcus aureus burden and number of IL-17-expressing T cells in the skin. Comparative skin microbiome analysis revealed that the clinical severity score was positively correlated with S. aureus (r=0.82), and negatively correlated with S. cohnii (r=-0.89). We found that monocolonization of the mice with S. aureus induced dermatitis (n=11, p<0.0001), whereas the mice kept under germ-free condition did not develop inflammation. We treated the mice by topical application with S. cohnii before or during development of dermatitis in order to characterize the therapeutic effect. Inoculation with specific S. cohnii strains significantly prevented S. aureus-driven dermatitis in the mice without affecting pathobiont burden (n=8, p<0.0001). In addition, human S. cohnii strain ameliorated dermatitis in the mice colonized with complex skin microbiota collected from AD patients (n=5-7, p<0.0001). S. cohnii also suppressed chemically-induced type 17 and type 2 immune-driven inflammation in pathobiont-independent manner. RNA-seq revealed that colonization with suppressive S. cohnii strain locally activated host glucocorticoid synthesis pathways and anti-inflammatory genes in the skin. Thus, specific S. cohnii strains have great potential as effective live biotherapeutics for diverse skin inflammation.

ESDR190 - Staphylococcus cohnii can alleviate diverse skin inflammation

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING