Dietary and Physiological Effects of Zinc on the Immune System

Abstract

Evidence for the importance of zinc for all immune cells and for mounting an efficient and balanced immune response to various environmental stressors has been accumulating in recent years. This article describes the role of zinc in fundamental biological processes and summarizes our current knowledge of zinc's effect on hematopoiesis, including differentiation into immune cell subtypes. In addition, the important role of zinc during activation and function of immune cells is detailed and associated with the specific immune responses to bacteria, parasites, and viruses. The association of zinc with autoimmune reactions and cancers as diseases with increased or decreased immune responses is also discussed. This article provides a broad overview of the manifold roles that zinc, or its deficiency, plays in physiology and during various diseases. Consequently, we discuss why zinc supplementation should be considered, especially for people at risk of deficiency. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Zinc Status Impacts the Epidermal Growth Factor Receptor and Downstream Protein Expression in A549 Cells

“…Moreover, we conclude from our data that the effects of alterations in zinc homeostasis upon E-cadherin and PD-L1 expression in non-stimulated cells cannot be entirely explained by zinc's impact on the EGFR. In fact, changes in PD-L1 expression and metabolism may additionally be attributed to the many other cellular processes that are regulated by zinc [64]. We propose that the zinc status impacts on the epidermal growth factor receptor's activity and surface expression but that the zinc status also acts independently of the EGFR upon its targets.…”

Zinc Levels Affect the Metabolic Switch of T Cells by Modulating Glucose Uptake and Insulin Receptor Signaling

“…Zinc as an essential trace element plays a crucial role in the immune system: zinc supplementation balances the immune function while a low serum zinc level during infections acts as a danger signal, activating immune cells. [31,47] Although the role of zinc in many aspects of the immune system has been revealed in the last decades, its impact on the metabolic switch of T cells is yet unknown. Thus, we set out to investi-gate the role of zinc using two in vitro models of T cell activation.…”

“…[28,29] In the contrary, a transient decrease of serum zinc concentration during acute phase reactions following a trauma or infection serves as a supportive danger signal for the immune system and improved immune responses. [30,31] Another aspect of how zinc interacts with cellular metabolism is its inhibitory effect on the mitochondrial function and the oxidative phosphorylation. In fact, an increase in zinc-binding metallothioneins and the enhanced release of zinc in the mitochondria modulates the respiratory complex I and III and thus in turn inhibits mitochondrial respiration.…”

An Appraisal of the Field of Metallomics and the Roles of Metal Ions in Biochemistry and Cell Signaling

“…Degenerative, metabolic and infectious/communicable diseases are all connected to the dyshomeostasis of metal metabolism, often in a causal rather than an effectual way. Zinc, in particular, is critically important for innate and adaptive immunity and hence adequacy and proper control are major factors for maintaining optimal immunity and regulating inflammation [44]. Zinc, therefore, has become a focus in the susceptibility to viral infections and their progression, as further evident in the present discussions of its role in the COVID-19 pandemic and in therapeutic approaches to the disease, though some of the underlying observations had been made many years ago [45,46].…”