Circadian protection against bacterial skin infection by epidermal CXCL14-mediated innate immunity

The epidermis is the outermost layer of the skin and the body's primary barrier to external pathogens; however, the early epidermal immune response remains to be mechaniskeratinocytes, exhibits robust circadian fluctuations and initiates innate immunity. Clearance of the skin pathogen Staphylococcus aureus in nocturnal mice was associated with CXCL14 expression, which was high during subjective daytime and low at night. In contrast, in marmosets, a diurnal primate, circadian CXCL14 expression was reversed. Rhythmically expressed CXCL14 binds to S. aureus DNA and induces inflammatory cytokine production by activating Toll-like receptor (TLR)9-dependent innate pathways in dendritic cells and macrophages underneath the epidermis. CXCL14 also promoted phagocytosis by macrophages in a TLR9-independent manner. These data indicate that circadian production of the epidermal chemokine CXCL14 rhythmically suppresses skin bacterial proliferation in mammals by activating the innate immune system.

Automated summary

The epidermis, the outermost layer of skin, acts as a primary barrier against external pathogens. The early immune response in the epidermis is still not well understood, but research has shown that keratinocytes exhibit circadian fluctuations and can activate innate immunity. In nocturnal mice, the expression of CXCL14, a chemokine, is associated with clearance of the skin pathogen Staphylococcus aureus, with high expression during the subjective daytime and low expression at night. However, in diurnal primates like marmosets, CXCL14 expression is reversed. These findings suggest that the circadian production of CXCL14 plays a role in suppressing skin bacterial proliferation by activating the innate immune system.