Immunological orchestration of zinc homeostasis: The battle between host mechanisms and pathogen defenses

The importance of Zn ions (Zn) in regulating development and functions of the immune system is well established. However, recent years have witnessed a surge in our knowledge of how immune cells choreograph Zn regulatory mechanisms to combat the persistence of pathogenic microbes. Myeloid and lymphoid populations manipulate intracellular and extracellular Zn metabolism via Zn binding proteins and transporters in response to immunological signals and infection. Rapid as well as delayed changes in readily exchangeable Zn, also known as free Zn and the Zn proteome are crucial in determining activation of immune cells, cytokine responses, signaling and nutritional immunity. Recent studies have unearthed distinctive Zn modulatory mechanisms employed by specialized immune cells and necessitate an understanding of the Zn handling behavior in immune responses to infection. The focus of this review, therefore, stems from novel revelations of Zn intoxication, sequestration and signaling roles deployed by different immune cells, with an emphasis on innate immunity, to challenge microbial parasitization and cope with pathogen insult.