The impact of metal availability on immune function during infection.

Nutrient transition metals are required cofactors for many proteins to perform functions necessary for life. As such, the concentration of nutrient metals is carefully maintained to retain critical biological processes while limiting toxicity. During infection, invading bacterial pathogens must acquire essential metals, such as zinc, manganese, iron, and copper, from the host to colonize and cause disease. To combat this, the host exploits the essentiality and toxicity of nutrient metals by producing factors that limit metal availability, thereby starving pathogens or accumulating metals in excess to intoxicate the pathogen in a process termed 'nutritional immunity'. As a result of inflammation, a heterogeneous environment containing both metal-replete and -deplete niches is created, in which nutrient metal availability may have an underappreciated role in regulating immune cell function during infection. How the host manipulates nutrient metal availability during infection, and the downstream effects that nutrient metals and metal-sequestering proteins have on immune cell function, are discussed in this review.