The role of keratinocytes in defense against infection

Abstract

The discovery of increasing numbers of epithelial antimicrobial peptides (AMPs), cytokines that specifically induce AMPs in epithelial cells, and mechanisms of its regulation point toward a central role of the keratinocyte as effector cell of the epithelial innate defense system. This review summarizes recent progress in understanding the keratinocyte's role in combating infection that can help to understand why skin is usually covered with microbes but normally not infected. The AMP LL-37 has been identified as regulator of keratinocyte apoptosis. The hypothesis of a direct defense function of keratinocytes, combating bacterial, fungal, virus and parasite infection, is strengthened. The discovery of an IL-22-producing T-lymphocyte subpopulation implicates a role in AMP induction of keratinocytes. Multiple studies are adding to our understanding of how skin keratinocytes are interacting in skin barrier defects and with the microflora. Although in atopic patients AMP production is not generally impaired, in hyperIgE syndrome a lack of Th17 cytokines causes local Staphylococcus aureus infection due to a defective keratinocyte defense system. Ultraviolet radiation induces AMPs and thus may have beneficial effects to combat skin infection. There is better understanding of the keratinocyte's role in the skin's innate defense system, and these data can help to generate therapeutics that can activate this defense system.