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By reducing immune function, trace metal deficiencies may substantially contribute to the global burden of diarrhea, pneumonia, and malaria. Human activities may be contributing to trace metal deficiency in soils and plants by exacerbating the preponderance of cereals and cash crops that reduce food diversity and micronutrient intake. Adaptive strategies are needed to reverse these trends. Anthropogenic activities have led to increased toxic metal exposure, and effects on human hosts need clarification. Metal toxicities can also impair the immune system and hence increase the susceptibility to infectious pathogens. Climate change affects metal speciation and the build-up of trace elements in the human food chain, with as yet unknown outcomes on infectious disease. Food processing and the use of metallic nanomaterials can alter human exposure to metals in ways that can influence the host–pathogen competition for metals. The effects of metals on human health may also be mediated through modification of the epigenome, conferring drug resistance on pathogenic bacteria and enhancing/ reducing human tolerance to infectious parasites. The emerging metals cerium, gadolinium, lanthanum, and yttrium constitute another driver of change in metal exposure and may potentially modulate the immune system with unknown consequences for human health.

Several metals play important roles in host cell and microbial metabolism because they form a part of central enzymes that are essential, for example, for DNA synthesis, cellular respiration, and key metabolic pathways. The availability of these metals differentially impact on host antimicrobial immune responses as well as on microbial defenses against them (Botella et al. 2012). Thus, during infection, host cells attempt to gain sufficient access to these metals or to limit the availability of these factors for microbes; this is thought to play a decisive role in the course of infections. Accordingly, subtle changes in the metabolism of these metals and their distribution throughout the body occur: microbes activate different pathways to secure a sufficient supply of these metals needed for their pathogenicity and proliferation as well as to mount effective defenses against the host immune system. This review focuses on the role of iron in the host–pathogen interplay. A brief discussion is included on the role of zinc, manganese, and copper for host–pathogen interaction, immune function, and their alteration by the inflammatory response.

Microbes must acquire metals for metabolic processes, with nearly a half of all enzymes requiring a metal cofactor for function, yet microbes can be poisoned by metals. The host innate immune defenses are thought to exploit these vulnerabilities to protect against invading pathogens, whereas microbes can respond by employing multiple strategies to maintain their metal homeostasis. Understanding these microbial strategies combined with knowledge of diverse metal challenges faced by different microbes in the various host niches could inform the development of new approaches for combating infectious diseases. This chapter summarizes extensive discussions on the interplay of metal ions in host–microbe interactions, from the microbial perspective. Focus is on five key areas: (a) how we define and determine metal availability, (b) the different levels and sources of metals available to microbes in different niches within the host, (c) the effect of the metal status of a pathogen, as derived from its prior environment, on its ability to establish an infection or the severity of disease, (d) the interplay between metals and the microbiota, and (e) how metal restriction and metal oversupply can kill or inhibit the growth of microbes.

Unhealthy lifestyle factors (e.g., cigarette smoking, excessive alcohol consumption, long working hours, reduced sleep, physical inactivity, obesogenic diets) and psychological stress contribute to cardiovascular disease, cancer, and other causes of mortality in industrialized countries. Many of these factors correlate with alterations in the homeostasis of trace metals, which play an important role in human health and are essential for human antioxidant defense and immune function. Metal levels consumed by humans are influenced by the mineral composition of soil used to grow food as well as weather conditions, the composition of irrigation water, and agricultural practices. In some cases, major sources of trace metals derive from environmental pollution that results from industrial and other anthropogenic activities. Food processing and packaging also play a role. Although primary exposure for some individuals happens in the workplace, most people encounter trace metals, both toxic and essential, through diet. Studies show that the most commonly metal-enriched foods are fish and seafood (mercury, copper, and zinc), vegetables and grains (cadmium, magnesium, and molybdenium), chocolate and coffee (cobalt, copper, and nickel), fruit (lead), nuts (selenium), and mushrooms (vanadium). This chapter discusses the impact of lifestyle on human exposure, homeostasis, and disease.