The emerging role of peptides and lipids as antimicrobial epidermal barriers and modulators of local inflammation

Abstract

Skin is complex and comprised of distinct layers, each layer with unique architecture and immunologic functions. Cells within these layers produce differing amounts of antimicrobial peptides and lipids (sphingoid bases and sebaceous fatty acids) that limit colonization of commensal and opportunistic microorganisms. Furthermore, antimicrobial peptides and lipids have distinct, concentration-dependent ancillary innate and adaptive immune functions. At 0.1-2.0 μM, antimicrobial peptides induce cell migration and adaptive immune responses to coadministered antigens. At 2.0-6.0 μM, they induce cell proliferation and enhance wound healing. At 6.0-12.0 μM, they can regulate chemokine and cytokine production and at their highest concentrations of 15.0-30.0 μM, antimicrobial peptides can be cytotoxic. At 1-100 nM, lipids enhance cell migration induced by chemokines, suppress apoptosis, and optimize T cell cytotoxicity, and at 0.3-1.0 μM they inhibit cell migration and attenuate chemokine and pro-inflammatory cytokine responses. Recently, many antimicrobial peptides and lipids at 0.1-2.0 μM have been found to attenuate the production of chemokines and pro-inflammatory cytokines to microbial antigens. Together, both the antimicrobial and the anti-inflammatory activities of these peptides and lipids may serve to create a strong, overlapping immunologic barrier that not only controls the concentrations of cutaneous commensal flora but also the extent to which they induce a localized inflammatory response.

Fig. 1

Immunohistochemical detection of antimicrobial peptides in epidermal layers of skin from normal subjects or subjects with infected or inflamed skin (compiled from other studies) [23, 24]. sl = Slight immunohistochemical detection. Note that some peptides are detected by immunohistochemistry in the stratum corneum, stratum granulosum, and stratum spinosum layers and less so in the stratum basale (e.g. HBD2, psoriasin, and RNase 7), whereas others are detected by immunohistochemistry to a lesser extent in the stratum corneum, but more so in the stratum granulosum, stratum spinosum, and in the stratum basale layers (e.g. HBD1).

Fig. 2

Various dose-dependent innate and adaptive immune functions of antimicrobial peptides. The specific concentrations and activities of antimicrobial peptides were compiled from other studies [33, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86].

Fig. 3

Various dose-dependent innate and adaptive immune functions of antimicrobial lipids. The specific concentrations and activities of antimicrobial lipids were compiled from other studies [65, 88, 89, 90, 91, 92, 93, 94, 95, 96].