1. 61: IL-20 receptor signaling inhibits cutaneous IL-1β and IL-17A production to promote methicillin-resistant staphylococcus aureus infection.
- Author
-
Datta, Sandip
- Subjects
- *
CELLULAR signal transduction , *INTERLEUKIN-1 , *INTERLEUKIN-17 , *PROMOTERS (Genetics) , *METHICILLIN-resistant staphylococcus aureus , *ETIOLOGY of diseases , *CYTOKINES - 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 STAT3-dependent 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 STAT3-dependent mechanisms that down-regulate IL-1 beta- and IL-17A-dependent inflammatory pathways required for control of infection. Inhibition of IL-1 beta by these cytokines was consistent with their demonstrated rapid inactivating sumoylation of C/EBP beta, a transcriptional activator of IL-1 beta. Similar effects of these cytokines were seen in human keratinocytes after S. aureus exposure, and antibody blockade of IL-20 receptor signaling improved infectious outcomes in mice. Our findings identify an immunosuppressive role for these cytokines during infection that may be therapeutically targeted to alter infectious susceptibility. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF