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Microbial killing inside macrophages andother phagocytes involves a variety ofmechanisms, including, for instance, acid-ication of the phagocytosis vacuole—orphagosome—and the production of toxicoxygen and nitrogen radicals (Flannaganet al., 2009). In addition, the immunemodulation of nutrients available formicrobial development in infected cellsand tissues is a re-emerging conceptreferred to as “nutritional immunity”(Weinberg, 1975). This concept mostlydeveloped from knowledge of the intra-cellular microbial starvation mechanisminvolving phagosomal iron and man-ganese depletion through the metaltransporter NRAMP (Hood and Skaar,2012). Growing evidence suggests thatimmune defense against microorganismsalsoinvolvesmicrobialkillingbytransitionmetals, such as zinc and copper, presentin excess in the microbial environment,and a set of recent reports showed thatseveral bacterial pathogens, such as thetuberculosis (TB) bacillus,

Zinc and copper toxicity in host defense against pathogens: Mycobacterium tuberculosis as a model example of an emerging paradigm