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Int. J. Mol. Sci. 2017, 18(10), 2197;

Metallothioneins: Emerging Modulators in Immunity and Infection

Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
Author to whom correspondence should be addressed.
Received: 29 September 2017 / Revised: 14 October 2017 / Accepted: 17 October 2017 / Published: 23 October 2017
(This article belongs to the Special Issue Zinc Signaling in Physiology and Pathogenesis)
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Metallothioneins (MTs) are a family of metal-binding proteins virtually expressed in all organisms including prokaryotes, lower eukaryotes, invertebrates and mammals. These proteins regulate homeostasis of zinc (Zn) and copper (Cu), mitigate heavy metal poisoning, and alleviate superoxide stress. In recent years, MTs have emerged as an important, yet largely underappreciated, component of the immune system. Innate and adaptive immune cells regulate MTs in response to stress stimuli, cytokine signals and microbial challenge. Modulation of MTs in these cells in turn regulates metal ion release, transport and distribution, cellular redox status, enzyme function and cell signaling. While it is well established that the host strictly regulates availability of metal ions during microbial pathogenesis, we are only recently beginning to unravel the interplay between metal-regulatory pathways and immunological defenses. In this perspective, investigation of mechanisms that leverage the potential of MTs to orchestrate inflammatory responses and antimicrobial defenses has gained momentum. The purpose of this review, therefore, is to illumine the role of MTs in immune regulation. We discuss the mechanisms of MT induction and signaling in immune cells and explore the therapeutic potential of the MT-Zn axis in bolstering immune defenses against pathogens. View Full-Text
Keywords: Metallothioneins; zinc; cytokines; signaling; infection; antimicrobial defenses; metals; nutritional immunity Metallothioneins; zinc; cytokines; signaling; infection; antimicrobial defenses; metals; nutritional immunity

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Subramanian Vignesh, K.; Deepe Jr., G.S. Metallothioneins: Emerging Modulators in Immunity and Infection. Int. J. Mol. Sci. 2017, 18, 2197.

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