Deficiency of Dermcidin-Derived Antimicrobial Peptides in Sweat of Patients with Atopic Dermatitis Correlates with an Impaired Innate Defense of Human Skin In Vivo

Abstract

Antimicrobial peptides are an integral part of the epithelial innate defense system. Dermcidin (DCD) is a recently discovered antimicrobial peptide with a broad spectrum of activity. It is constitutively expressed in human eccrine sweat glands and secreted into sweat. Patients with atopic dermatitis (AD) have recurrent bacterial or viral skin infections and pronounced colonization with Staphylococcus aureus. We hypothesized that patients with AD have a reduced amount of DCD peptides in sweat contributing to the compromised constitutive innate skin defense. Therefore, we performed semiquantitative and quantitative analyses of DCD peptides in sweat of AD patients and healthy subjects using surface-enhanced laser desorption ionization time-of-flight mass spectrometry and ELISA. The data indicate that the amount of several DCD-derived peptides in sweat of patients with AD is significantly reduced. Furthermore, compared with atopic patients without previous infectious complications, AD patients with a history of bacterial and viral skin infections were found to have significantly less DCD-1 and DCD-1L in their sweat. To analyze whether the reduced amount of DCD in sweat of AD patients correlates with a decreased innate defense, we determined the antimicrobial activity of sweat in vivo. We showed that in healthy subjects, sweating leads to a reduction of viable bacteria on the skin surface, but this does not occur in patients with AD. These data indicate that reduced expression of DCD in sweat of patients with AD may contribute to the high susceptibility of these patients to skin infections and altered skin colonization.

Antimicrobial Peptides, Skin Infections, and Atopic Dermatitis

“…106 It is constitutively expressed in eccrine sweat glands and secreted into sweat. Several dermcidin derived peptides are significantly reduced in AD compared to healthy subjects, and atopics with previous bacterial or viral infections show the lowest concentration.…”

Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor

“…Patients with atopic dermatitis are much more prone to skin infections than patients with psoriasis. This difference has now been linked to the high expression of AMPs in psoriasis compared with atopic dermatitis (9)(10)(11).…”

Structure-Activity Analysis of the Dermcidin-derived Peptide DCD-1L, an Anionic Antimicrobial Peptide Present in Human Sweat

“…The 110-amino acid precursor is proteolytically processed in sweat, giving rise to several truncated DCD peptides differing in length and charge (14 -16). Evidence for a clinical relevance of DCD peptides came from our previous studies indicating that patients with atopic dermatitis have a reduced amount of DCD peptides in sweat which contributed to the high susceptibility of these patients to skin infections and to altered bacterial skin colonization (17).…”