The Mechanism By Which IL-17D Reduces Camp To Aggravate Staphylococcus Aureus Skin Infection Via Inhibiting Adipogenesis

It is known that IL-17A,IL-17C and IL-17F,three members of IL-17 cytokine family,can regulate host immune responses against Staphylococcus aureus(S.aureus)skin infections.However,whether IL-17 D,a member of IL-17 cytokine family,would regulate host defense against S.aureus skin infection remains completely unknown.To analyze the fuction of IL-17D during S.aureus skin infection,we infected wild-type and Il17d–/– mice with S.aureus.3 days later,we analyzed the bacterial load of S.aureus and found that the defiency of Il17 d in mice significantly reduced the survival of S.aureus in mouse skin,which accompanied with smaller lesional sizes.These data demonstrate that IL-17 D aggravates S.aureus skin infection in mice.To dessect how IL-17D inhibits host defense to increase S.aureus skin infection,IL-17 D was overexpressed and the antimicrobial factors were evaluated.However,IL-17 D did not induce i NOS expression in macrophages and REG3 A in keratinocytes.To our surprise,IL-17 D inhibited the antimicrobial peptide Camp in preadipocytes.Moreover,we found that IL-17 D inhibited Camp via inhibiting the expression of adipogenesis transcription factors includinig CEBPα and PPARγ,thus exacerbating S.aureus skin infection.Altogether,our data demonstrate that IL-17 D downregulates Camp expression to aggravate S.aureus skin infection via inhibiting adipogenesis.To our knowledge,our findings show for the first time that IL-17 D dampens antimicrobial defense to aggravate S.aureus skin infecton,and provide new insights into the treatment of S.aureus infection in the skin.