The Metallothionein-Zinc Landscape: How It Shapes Antimicrobial Immunity

Abstract

Nutritional immunity refers to the ability of the host to sequester nutrients from pathogens during infection. Metal ions are important for microbial survival and pathogenesis as well as for host defenses. For example, while zinc (Zn2+) is crucial for microbial fitness within the host, immune cells deprive microbes of these metal ions and retain it for their own defense. However, excess Zn2+ may be toxic to both the host and the pathogen. Therefore, Zn2+ regulation is a central component of host-pathogen interactions and antimicrobial immunity. Metallothioneins (MTs) are a family of highly conserved cysteine-rich proteins that are ubiquitously expressed in most organisms. Immune cells express MTs in response to a variety of stimuli including cytokines, chemokines, and infectious agents. They regulate intracellular Zn2+ homeostasis, protect from oxidative stress, and modulate host immunity during infection. Although Zn2+ signals are well known to alter immunological processes, our knowledge of how the MTs-Zn2+ axis affects immune response to infections is relatively scarce. Emerging evidence points to a significant role for MTs in regulating host immunity. Thus, this chapter discusses immunomodulatory roles of MTs with a focus on Zn2+ regulation in response to pathogen attack.