Signaling via The IL-20 Receptor Inhibits Cutaneous Production of IL-1β and IL-17A to Promote Infection with Methicillin-Resistant Staphylococcus Aureus

August 14, 2013

Ian A Myles, Natalia M Fontecilla, Patricia A Valdez, Paul J Vithayathil, Shruti Naik, Yasmine Belkaid, Wenjun Ouyang, Sandip K Datta

Nature Immunology

Staphylococcus aureus causes most infections of human skin and soft tissue and is a major infectious cause of mortality. Host defense mechanisms against S. aureus are incompletely understood. Interleukin 19 (IL-19), IL-20 and IL-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 found here that those cytokines promoted cutaneous infection with S. aureus in mice by downregulating IL-1β- and IL-17A-dependent pathways. We noted similar effects of those cytokines in human keratinocytes after exposure to S. aureus, and antibody blockade of the IL-20 receptor improved outcomes in infected mice. Our findings identify an immunosuppressive role for IL-19, IL-20 and IL-24 during infection that could be therapeutically targeted to alter susceptibility to infection.