Interplay of innate and adaptive immunity in metal-induced hypersensitivity

Abstract

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.

Old and new adjuvants

“…Other insoluble metal salts such as beryllium hydroxide, have adjuvant properties that enhance sensitization and disease after pulmonary exposure [55]. Beryllium hydroxide induces release of caspase-1-independent IL-1α from necrotic alveolar macrophages and mediates its adjuvant effects on Th1 cells via MyD88-dependent receptors that enhance DC migration and function [56].…”

Cheongsangbangpung-tang ameliorated the acute inflammatory response via the inhibition of NF-κB activation and MAPK phosphorylation

“…Homeostasis of the human body can be maintained with proper control of the immune response. In addition, an abnormal or overactive immune system can cause pathogenic conditions, such as asthma, autoimmunity and hypersensitivity [6, 7]. …”

A role for TNF-α in alveolar macrophage damage-associated molecular pattern release

“…Treatment of Be-exposed mice with neutralizing anti-TNF-α antibodies impairs IL-1α-dependent recruitment of neutrophils into the airways and mobilization of immunogenic pulmonary cDCs from the lung to the LDLNs. Neutrophil recruitment in Be-exposed mice is driven by IL-1α in Be-exposed mice with no evidence of a role for caspase-1, NALP3, or IL-1β (2,36). Therefore, we predicted that neutrophil entry into the airways of Be-exposed mice would be attenuated by anti-TNF-α treatment.…”

“…We have shown that AM cell death and DAMP release occur following single low-dose exposures to either beryllium sulfate (which forms beryllium hydroxide in airway fluids) or crystalline beryllium hydroxide (Be) particles (2). DNA and IL-1α released from Be-exposed AMs induce upregulation of CD80 on cDCs via the MyD88-dependent receptors TLR9 and IL-1R1 (2,12,36). In addition, DNA released by Be-exposed AMs promotes accelerated migration of cDCs from the lung to the LDLNs via TLR9 (2).…”