Interplay of innate and adaptive immunity in metal-induced hypersensitivity

Metal-induced hypersensitivity is driven by T cell sensitization to metal ions. Recent advances in our understanding of the complex interactions between innate and adaptive immunity have expanded our knowledge of the pathogenesis of these diseases. Metals activate the innate immune system through direct binding to pathogen recognition receptors, activation of the inflammasome, or the induction of cellular death and release of alarmins. Certain metals can serve as adjuvants, promoting dendritic cell activation and migration as well as antigen presentation to metal-specific T cells. These T cells can recognize metals as haptens or as altered MHC-peptide complexes. The ability of metals to create these neoantigens emphasizes the similarity between metal-induced hypersensitivity and autoimmunity.