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

Staphylococcus aureus causes the majority of human skin and soft tissue infections, and is a major infectious cause of mortality. 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 are associated with inflammatory skin diseases such as psoriasis and atopic dermatitis. We show here that these cytokines promote cutaneous S. aureus infection in mice by downregulating IL-1β- and IL-17A-dependent pathways. Similar effects of these cytokines were seen in human keratinocytes after S. aureus exposure, and antibody blockade of IL-20 receptor improved outcomes in infected mice. Our findings identify an immunosuppressive role for these cytokines during infection that could be therapeutically targeted to alter susceptibility to infection.