Zinc Sequestration: Arming Phagocyte Defense against Fungal Attack

The innate immune system employs various defense mechanisms to combat invading microbes. From a pathogen perspective, access to adequate nutrition is one of the fundamental requirements for survival within the host. The ability to counter microbial survival by restricting basic elements of growth, extending from amino acids to sugars and metals, is referred to as nutritional immunity [1]. The mechanisms of Zn acquisition, transport, and storage have been investigated in both prokaryotic and eukaryotic systems. In this review, the total amount of zinc regardless of its chemical form will be referred to as Zn, and the labile fraction as Zn2+. From an immunological perspective, the primary focus has been on the impact of Zn regulation on the numbers and function of lymphocytes and phagocytes and their correlation with susceptibility to infections, but a dissection of the molecular details in these processes has been lacking. More recently, understanding the Zn modulatory mechanisms and how they drive host-pathogen interactions at the molecular level has been a subject of intense scrutiny. This review will accentuate existing and novel insights into the roles of Zn in nutritional immunity and in phagocyte defenses against fungi.