Skin Staphylococcus species differentially modulate keratinocyte cytokine secretion in response to UVB

Skin acts as the body's first line of defense against environmental insults including ultraviolet radiation (UVR) from sunlight and engages in a dynamic dialog with the resident skin microbiota, increasingly recognized for its role in shaping and educating the immune responses of the skin in both health and disease. However, how or indeed if the resident skin microbiota mediates inflammatory responses to sunlight remains unclear. To address this, we investigated the effects of five abundant members of the skin microbiota on cytokine secretion in human primary keratinocytes exposed to a single dose of UVB. Co-culture of primary keratinocytes with a defined five-species skin commensal community resulted in a broad increase in the secretion of innate immune mediators including interleukin-6 (IL-6), independent of UVB exposure. In the absence of UVB, Staphylococcus epidermidis was the dominant species, followed by Staphylococcus hominis within the five-species community. UVB induced a marked shift in community composition, characterized by increased proliferation of S. hominis and reduced S. epidermidis abundance, as confirmed by species-specific growth curve analyses. Assessment of species-specific effects using mono-associated host cells revealed S. epidermidis as the predominant contributor to the enhancement of immune mediator secretion. Without the presence of additional community members, UVB amplified S. epidermidis-induced cytokine secretion. However, co-culture of S. epidermidis with S. hominis attenuated the heightened inflammatory response to UVB typically associated with S. epidermidis, likely due to the reduced abundance of S. epidermidis following UVB exposure. These findings suggest that the resident skin microbiota may contribute to our inflammatory response to sunlight.IMPORTANCEThis study reveals that the skin microbiome may play a role in shaping inflammatory responses to UVB exposure. It provides evidence of organisms capable of both amplifying and mitigating inflammatory responses to UVB, highlighting the importance of microbial composition in photoprotection. These findings suggest individual responses to sunlight may be influenced not only by skin type but also by specific microbes present on the skin.