Abstract & Commentary
Synopsis: Skin affected by atopic dermatitis fails to express antimicrobial peptides, possibly accounting for the almost universal presence of S aureus in these lesions.
Source: Ong PY, et al. Endogenous antimicrobial peptides and skin infection in atopic dermatitis. N Engl J Med. 2002; 347:1151-1160.
Ong and colleagues in Denver, San Diego, and Los Angeles evaluated the role of endogenous antimicrobial peptides in protection against Staphylococcus aureus infection of the skin by examining the concentrations of cathecidins (LL-37) and human ß-defensin 2 (HBD-2) in skin biopsy samples from 8 patients with atopic dermatitis, 11 with psoriasis, and 6 healthy controls. Relative to patients with psoriasis, the concentration of both of these peptides was significantly reduced in both acute and chronic lesions of patients with atopic dermatitis, as was the expression of their relevant mRNAs. LL37 and HBD-2 were not detected in normal skin. In vitro studies demonstrated that LL-37 and HBD-2 synergistically killed S aureus.
Comment by Stan Deresinski, MD, FACP
Up to 100% of patients with atopic dermatitis exhibit cutaneous colonization with S aureus.1 While the pathophysiology of atopic dermatitis is poorly understood, production of a variety of staphylococcal toxins, especially those that act as superantigens have been suggested to play a role in contributing to the severity of the dermatitis.2 In contrast, psoriasis is not associated with a significantly increased risk of staphylococcal infection.
The endogenous antimicrobial peptides are a part of the innate immune system and, among other things, act as a defense at our mucocutaneous interface with the outside world. Targeting the microbial cell membrane, they are variably active against some bacteria, fungi, and enveloped viruses. HBD-2, originally discovered in psoriatic lesional skin and expressed in ketinocytes associated with inflammatory cutaneous lesions, has potent activity against many Gram-negative bacteria and Candida spp., but does not have significant activity against S aureus.3 This resistance appears to be related to the expression of a novel gene by this organism, mpfR, which is associated with a reduced negative membrane charge that presumably repulses the cationic antimicrobial peptides.4 The study discussed here, however, demonstrates synergistic killing of S aureus at concentrations contained in psoriatic skin. Cathelicidins such as LL-37 appear to have characteristics similar to those of defensins and both types of protein also have chemotactic activity.
Thus, this study demonstrates that these cationic proteins are not expressed in normal skin, but are upregulated in psoriatic lesional skin. Atopic skin, despite the presence of inflammation and, almost invariably, S aureus, also fails to express these antimicrobial proteins, demonstrating an apparent failure of the innate immune system.
The role played by S aureus in atopic dermatitis remains unclear. As many as two thirds of associated strains produce superantigens, products that have been suggested, but not proven, to contribute to the pathophysiology of the disease. It would also be of interest to know the potential role of the Panton-Valentin leukocidin in this process.
Dr. Deresinski, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor of Infectious Disease Alert.
References
1. Breuer K, et al. Staphylococcus aureus: Colonizing features and influence of an antibacterial treatment in adults with atopic dermatitis. Br J Dermatol. 2002; 147:55-61.
2. Zollner TM, et al. Colonization with superantigen-producing Staphylococcus aureus is associated with increased severity of atopic dermatitis. Clin Exp Allergy. 2000;30:994-1000.
3. Schroder JM, Harder J. Human beta-defensin-2. Int J Biochem Cell Biol. 1999;31:645-651.
4. Peschel A, Jack RW, Otto M, Collins LV, et al. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with l-lysine. J Exp Med. 2001;193:1067-1076.
Skin affected by atopic dermatitis fails to express antimicrobial peptides, possibly accounting for the almost universal presence of S aureus in these lesions.
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