Metal ions in macrophage antimicrobial pathways: emerging roles for zinc and copper

Abstract

The immunomodulatory and antimicrobial properties of zinc and copper have long been appreciated. In addition, these metal ions are also essential for microbial growth and survival. This presents opportunities for the host to either harness their antimicrobial properties or limit their availability as defence strategies. Recent studies have shed some light on mechanisms by which copper and zinc regulation contribute to host defence, but there remain many unanswered questions at the cellular and molecular levels. Here we review the roles of these two metal ions in providing protection against infectious diseases in vivo, and in regulating innate immune responses. In particular, we focus on studies implicating zinc and copper in macrophage antimicrobial pathways, as well as the specific host genes encoding zinc transporters (SLC30A, SLC39A family members) and CTRs (copper transporters, ATP7 family members) that may contribute to pathogen control by these cells.

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

“…Moreover, recent literature has revealed that ZnT and ZIP transporters are involved in novel functions of zinc in immunity, "nutritional immunity" (384,388), as in the case of transporters of other nutritional metals such as iron (360). Here, the microbial pathogen is starved of micronutrients through spatial isolation (164).…”

Copper Resistance of the Emerging Pathogen Acinetobacter baumannii

“…Such a strategy may make a very limited amount of copper very effective against infection. The human immune system utilizes copper in various ways to fight infection, and concentrations upwards of 500 M have been measured in macrophage phagosomes (54)(55)(56). Furthermore, methods of increasing the concentration of copper in the body to enhance its antimicrobial effects are being investigated (57)(58)(59)(60).…”

Remodelamento metabólico de Paracoccidioides lutzii durante a privação de cobre determinado por análises proteômicas

“…A proteína ATP7A, uma ATPase tipo P localizada primariamente no complexo do Golgi, está envolvida no metabolismo de cobre e é responsável pela exportação de cobre quando as células são expostas a altas concentrações deste metal, também podendo transportar este metal em vesículas ou compartimentos intracelulares (Lutsenko et al, 2007;Stafford et al, 2013).…”

“…Mais de 95% do cobre presente no plasma está ligado à CP, logo esta proteína possui grande importância para a homeostase deste metal (Stafford et al, 2013). Além da alta afinidade a cobre, CP também pode atuar como oxidase de ferro, catalizando a oxidação de Fe +2 a Fe +3 , tendo assim importante papel na homeostase de ferro (Osaki e Johnson, 1970).…”

“…Além da alta afinidade a cobre, CP também pode atuar como oxidase de ferro, catalizando a oxidação de Fe +2 a Fe +3 , tendo assim importante papel na homeostase de ferro (Osaki e Johnson, 1970). Além disso, vários estímulos pró-inflamatórios, incluindo IFN-γ, IL-1, IL-6, TNF-α e lipopolissacarídeo (LPS), induzem a sua síntese (Stafford et al, 2013).…”