Innate barriers against skin infection and associated disorders

Abstract

The innate immune system is primarily responsible for prevention of infection of the skin by pathogens, but is also important in control of inflammation. The components of innate immunity are frequently misunderstood based on a historical bias for leukocyte-mediated immune defense. Many participating cell types are often overlooked, in particular epithelial cells that provide an early and critical step to innate immune defense. This review will discuss our epithelial barrier to infection with emphasis on how microbes subvert this system, and human diseases associated with these events.

Functions of the skin microbiota in health and disease

“…These epithelial cells express a number of pattern recognition receptors (PRRs) that sense microbes through recognition of conserved molecular entities such as lipoproteins, nucleic acids, cell wall components, and flagella. While keratinocytes express a number of antimicrobial peptides, cytokines, and chemokines at steady state, activation of PRRs can rapidly increase the expression these molecules, resulting in direct antimicrobial effects as well as recruitment and education of additional immune cells [31]. Also found in the epidermis are Langerhans cells (LCs), a specific subset of dendritic cells.…”

Inducible Innate Resistance of Lung Epithelium to Infection

“…Research on interactions of the coagulation system with lung epithelial cells has focused primarily on mesothelial cells of the pleural space in fibrinolysis, permeability changes of the alveolar epithelium in diffuse lung injury, and occlusion of distal airways in asthma (95-97), while the role of the coagulation system in inducible resistance is mostly unknown. The kallikrein-kinin cascade is co-activated with the complement and coagulation cascades, generating potent inflammatory mediators whose role in inducible resistance is yet unknown, and activating cathelicidin (98) that likely participates in inducible resistance (see below).…”

“…Indeed, epithelial barrier functions are modulated both by pathogens and as part of the host response, presenting a dynamic situation during infection. The different strategies utilized by microbial pathogens to breach epithelial barriers have been discussed in several recent reviews (98, 111-114). Here we focus on inducible barrier function.…”

“…Pathogens at a variety of mucosal surfaces enter epithelial cells to invade underlying tissues (22, 98, 112). This pathogenic mechanism is counteracted by epithelial exfoliation.…”

“…Lung pathogens release a wide array of toxins and exoenzymes capable of killing lung epithelial cells and allowing microbial penetration (22, 98, 112). Further, viral injury of lung epithelium allows bacterial penetration that appears to be an important cause of mortality (126).…”