The role of microorganisms in atopic dermatitis

Abstract

Atopic dermatitis (AD) is a common, fluctuating skin disease that is often associated with atopic conditions such as asthma and IgE-mediated food allergy and whose skin lesions are characterized by a Th-2 cell-mediated response to environmental antigens. The increasing prevalence and severity of atopic diseases including AD over the last three decades has been attributed to decreased exposure to microorganisms during early life, which may result in an altered Th-1/Th-2-balance and/or reduced T cell regulation of the immune response. Patients with AD exhibit defects in innate and acquired immune responses resulting in a heightened susceptibility to bacterial, fungal and viral infections, most notably colonization by S. aureus. Toxins produced by S. aureus exacerbate disease activity by both the induction of toxin-specific IgE and the activation of various cell types including Th-2 cells, eosinophils and keratinocytes. Allergens expressed by the yeast Malazessia furfur, a component of normal skin flora, have also been implicated in disease pathogenesis in a subset of AD patients. Microorganisms play an influential role in AD pathogenesis, interacting with disease susceptibility genes to cause initiation and/or exacerbation of disease activity.

Fig. 1

Two possible mechanisms for the increased prevalence of allergy as a result of decreased exposure to microbial antigens.

Fig. 2

Defective innate immunity in AD skin.Altered intracellular and extracellular PRR expression, and decreased antimicrobial molecule production (partly due to inhibition by Th-2 cytokines) results in an impaired innate immune response to microorganisms, which gain entry to the epidermis as a result of an altered barrier function. HBD-2/HBD-3, human β-defensin-2/3; LL-37, a member of the cathelicidin family; iNos, induced nitric oxide synthetase.