Innate Immune System Response in Metal Allergy: Toll-Like Receptors

Chapter

Abstract

Sensitization is a prerequisite for the development of allergic contact dermatitis. Its initiation, however, is—as mistakenly assumed for quite a while—not just dependent on an adaptive immune response, but also requires a supplementary signal that activates the innate immune system. Many metal allergens are capable of delivering both signals—the mandatory antigenic stimulus and an innate proinflammatory signal. In recent years, the molecular mechanisms of metal-induced innate immune activation have at least in part been deciphered. It turned out that nickel, cobalt and presumably palladium directly bind to Toll-like receptor 4 (TLR4) in humans, resulting in receptor dimerization, activation and subsequent gene transcription. On the other hand, metal compounds may injure cells and tissue leading to alteration of extracellular matrix molecules such as hyaluronan, which can serve as endogenous ligands for TLRs. Additionally, metal haptens may induce reactive oxygen species (ROS) that result in activation of the inflammasome, a multimeric protein platform that controls release of the proinflammatory cytokines IL-1β and IL-18. A recently identified powerful activator of the inflammasome is the widespread contact hapten dichromate. Importantly, TLR and inflammasome activation may occur at the same time and collaborate in delivering innate immune signals. Finally, the coincident presence of microbial pathogens that can activate TLRs may support the development of contact allergies to metals. A better understanding of the mechanisms by which metal allergens are sensed by the innate immune system may contribute to the design of novel therapeutic approaches for this common allergic disease.

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of DermatologyUniversity Hospital WürzburgWürzburgGermany

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