IL-20 receptor signaling inhibits cutaneous IL-1 beta and IL-17A production to promote methicillin-resistant Staphylococcus aureus infection

Abstract Staphylococcus aureus causes the majority of human skin and soft tissue infections, and is a major infectious cause of mortality. However, host defense mechanisms against S. aureus are incompletely understood. Interleukin (IL)-19, -20 and -24 signal through type I and type II IL-20 receptors and have been associated with inflammatory skin diseases such as psoriasis and atopic dermatitis. We hypothesized these cytokines may play a role in S. aureus skin infections. We show here that this family of cytokines promotes cutaneous S. aureus infection in mice by downregulating IL-1β- and IL-17A-dependent inflammatory pathways required for control of infection. Our findings identify an immunosuppressive role for these cytokines during infection, and suggest these pathways may contribute to infectious susceptibility.