Metallothionein: a Potential Link in the Regulation of Zinc in Nutritional Immunity Mohammad Tariqur Rahman 1 & Muhammad Manjurul Karim 2 Received: 7 April 2017 /Accepted: 22 May 2017 # Springer Science+Business Media New York 2017 Abstract Nutritional immunity describes mechanisms for withholding essential transition metals as well as directing the toxicity of these metals against infectious agents. Zinc is one of these transition elements that are essential for both humans and microbial pathogens. At the same time, Zn can be toxic both for man and microbes if its concentration is higher than the tolerance limit. Therefore a Bdelicate^ balance of Zn must be maintained to keep the immune cells surveilling while making the level of Zn either to starve or to intoxicate the pathogens. On the other hand, the invading pathogens will exploit the host Zn pool for its survival and replication. Apparently, different sets of protein in human and bacteria are involved to maintain their Zn need. Metallothionein (MT)—a group of low molecular weight proteins, is well known for its Zn-binding ability and is expected to play an important role in that Zn balance at the time of active infec- tion. However, the differences in structural, functional, and molecular control of biosynthesis between human and bacte- rial MT might play an important role to determine the proper use of Zn and the winning side. The current review explains the possible involvement of human and bacterial MT at the time of infection to control and exploit Zn for their need. Keywords Inflammation . Glucocorticoid hormone . Metallothionein . Metalloproteases . Nutritional immunity . Zinc toxicity Introduction To prevent pathogenesis of infectious microorganisms, humans restrict access to essential metals in a process known as nutritional immunity. Broadly, nutritional immunity de- scribes mechanisms for withholding essential transition metals as well as directing the toxicity of these metals against infectious agents. Scope of nutritional immunity has broaden from its original concept of referring to iron (Fe) to include other transition metals such as zinc (Zn), copper (Cu), and manganese (Mn) [1]. While Fe and Cu are known to have redox potential and are involved in large number of oxidore- ductases or other electron transfer proteins, Zn plays critical role in structural as well as catalytic proteins both in eukary- otes and prokaryotes [2]. Zn is frequently incorporated into metalloenzymes, storage proteins, and transcription factors and become the second most abundant transition metal in most living systems after Fe. For example, ∼80% enzymes in archaea and bacteria are Zn-containing proteins while those in eukaryotes are ∼50%. However, Zn-binding proteins, in- cluding Zn-dependent transcription factors, make up a larger proportion of the total proteome in eukaryotes as compared to bacteria and archaea [3]. Thus, Zn is essential for both humans and microbial pathogens to survive. At the same time, Zn can be toxic if its concentration is higher than the tolerance limit both for man and microbes. Cells of the human body use a number of sophisticated mechanisms to maintain intracellular and extracellular Zn ho- meostasis. Role of Zn in life processes has been thoroughly reviewed [4–6]. Dietary Zn deficiency results in loss of im- mune function and resistance to infection suppressing thymic function, T lymphocyte development, lymphocyte prolifera- tion, and T cell-dependent B cell functions [7]. At the same time, to acquire the required amount of Zn in Zn-deficient conditions and to prevent lethal effects of Zn in Zn excess * Mohammad Tariqur Rahman m.tariqur.rahman@gmail.com; tarique@um.edu.my 1 Faculty of Dentistry, University of Malaya, Kula Lumpur 50603, Malaysia 2 Department of Microbiology, University of Dhaka, Dhaka 1000, Bangladesh Biol Trace Elem Res DOI 10.1007/s12011-017-1061-8