Innate Immune Functions of the Keratinocytes

Human keratinocytes are known to kill living microbes. They express different pattern recognition receptors (PRRs) such as the Toll-like receptor 2 (TLR2), TLR4, the CD1d molecule and a keratinocyte mannose-binding receptor (KcMR). In response to challenge with microbes or microbial-derived substances the activation and nuclear translocation of NF-kappaB, the production of nitric oxide (NO) and inflammatory cytokines occur in keratinocytes, in a TLR-dependent manner. Blocking of NF-kappaB activation or NO production inhibit the Candida albicans-killing activity of keratinocytes. This Candida killing activity could be inhibited by blocking of KcMR. Recognition of invading pathogens in the epidermis triggers cytokine production in keratinocytes leading to elimination of pathogens and the activation of the adaptive immune system. These findings stress the importance of the role of keratinocytes in innate immunity.