The Molecular Mechanisms By Which Commensal Bacterium Staphylococcus Epidermidis Modulates Propionibacterium Acnes-induced Inflammation

Skin is an effective physical and chemical barrier against the external environment. In addition, skin provides a habitat for hundreds of millions of microorganisms. Staphylococcus epidermidis (S.epidermidis), as one of the most common skin commensal, plays essential roles in host defenses against pathogens. Propionibacterium acnes (P.acnes), as a pathogen, is closely related to the occurrence and development of acne. It has been reported that Propionibacterium acnes, the culprit of acne vulgaris, can activate TLR2to induce proinflammatory cytokine expression. However, the mechanism by which P.acnes induces inflammation and the role of the skin commensal in modulating this inflammation remains unknown.In our study heat-inactivated P.acnes was used to stimulate keratinocytes and macrophages, respectively. Our results demonstrate that in addition to TLR2, TLR2’s co-receptor CD14and CD36were involved in P. acnes-induced inflammation. To induce the expression of inflammatory cytokines P.acnes further activated p38and NF-κB signaling pathways in keratinocytes, while in macrophages P.acnes induced inflammatory responses by activating ERK, Akt, p38and NF-κB pathways.Previously we have reported that skin commensal Staphylococcus epidermidis can suppress TLR3-dependent inflammation after skin injury. To test whether if Staphylococcus epidermidis could suppress P. acnes-induced inflammatory responses, we used<10-kDa product of S.epidermidis (SECM) to pretreat keratinocytes and then stimulate with P.acnes.We found that SECM significantly inhibited P.acnes-induced TNF-a and IL-6expression in karetinocytes. Furthermore, we identified that Lipoteichoic acid (LTA) was the active component among that<10-kDa products of SECM. Administration of SECM or LTA also significantly attenuated the proinflammatory cytokines production in mice ear. LTA reduced p.acnes-induced proinflammatory cytokines expression by down-regulating TLR2and CD14expression, thus leading to decreased MAPKs and NF-κB activation. However, in RAW264.7cells, S.epidermidis failed to regulate P.acnes-induced inflammatory response. Taken together, our results for the first time show that commensal bacterium S.epidermidis could modulate P.acnes-induced proinflammatory cytokines in keratinocytes. These findings provide new evidence of the beneficial roles of commensal bacterium on skin and new insights into the treatment of acne.