Peptides antimicrobiens naturels cutanés Innate antimicrobial peptides in the skin

Résumé

Une des stratégies majeures mises en jeu par la peau pour se protéger des infections est de maintenir une barrière physique cutanée intacte. La désquamation, de même que la sécrétion de mucus, sont à l’origine d’un renouvellement permanent de la surface cutanée, qui s’accompagne d’une élimination des micro-organismes adhérant à cette surface. La découverte récente de peptides antibiotiques épithéliaux suggère qu’il existe, à côté de cette barrière physique, une barrière cutanée « chimique » constituée par des peptides antibiotiques capables de contrôler la croissance bactérienne au niveau des couches cutanées et, éventuellement, de lutter contre les infections.

Summary

Human skin is always in contact with the environment and is covered with a characteristic microflora, but it is usually not infected. Although desquamation and secretion of mucus lead to a permanent renewal of these body surfaces and simultaneous elimination of microorganisms adhering to these layers, another reason for this natural resistance might be the existence of a “chemical barrier” consisting in constitutively and inducibly produced antimicrobial peptides and proteins (AMPs), which include some ß-defensins, RNase 7, the S100-protein psoriasin and the cathelicidin LL-37. Most of these AMPs can be induced in vitro in epithelial cells by proinflammatory cytokines or bacteria. In vivo, AMPs are mainly expressed in uppermost and differentiated parts of inflammatory lesions and wounds, but some are also focally expressed in skin in the absence of inflammation, suggesting that apart from inflammatory mediators, also non-inflammatory stimuli of endogenous and/or exogenous origin can stimulate AMP-synthesis. Increased levels of AMPs in psoriatic lesions may explain why psoriasis patients rarely suffer from skin infections. Further, an increased infection rate in atopic dermatitis patients could be the consequence of decreased levels of AMPs in atopic lesions. These observations may indicate an important role of the “chemical skin barrier” in prevention of skin infection and suggest that artificial stimulation of this system, without inflammation, would be beneficial as « immune stimulus ».