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Int. J. Mol. Sci. 2017, 18(11), 2375; https://doi.org/10.3390/ijms18112375

Elemental Ingredients in the Macrophage Cocktail: Role of ZIP8 in Host Response to Mycobacterium tuberculosis

1
Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA
2
Texas Biomedical Research Institute, San Antonio, TX 78227, USA
3
Center for Pharmacogenomics, Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43085, USA
4
College of Pharmacy, The University of Nebraska Medical Center, Omaha, NE 68198-6120, USA
*
Authors to whom correspondence should be addressed.
Received: 6 October 2017 / Revised: 1 November 2017 / Accepted: 6 November 2017 / Published: 9 November 2017
(This article belongs to the Special Issue Zinc Signaling in Physiology and Pathogenesis)
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Abstract

Tuberculosis (TB) is a global epidemic caused by the infection of human macrophages with the world’s most deadly single bacterial pathogen, Mycobacterium tuberculosis (M.tb). M.tb resides in a phagosomal niche within macrophages, where trace element concentrations impact the immune response, bacterial metal metabolism, and bacterial survival. The manipulation of micronutrients is a critical mechanism of host defense against infection. In particular, the human zinc transporter Zrt-/Irt-like protein 8 (ZIP8), one of 14 ZIP family members, is important in the flux of divalent cations, including zinc, into the cytoplasm of macrophages. It also has been observed to exist on the membrane of cellular organelles, where it can serve as an efflux pump that transports zinc into the cytosol. ZIP8 is highly inducible in response to M.tb infection of macrophages, and we have observed its localization to the M.tb phagosome. The expression, localization, and function of ZIP8 and other divalent cation transporters within macrophages have important implications for TB prevention and dissemination and warrant further study. In particular, given the importance of zinc as an essential nutrient required for humans and M.tb, it is not yet clear whether ZIP-guided zinc transport serves as a host protective factor or, rather, is targeted by M.tb to enable its phagosomal survival. View Full-Text
Keywords: zinc; zinc transporter; tuberculosis; lung; macrophage; innate immunity zinc; zinc transporter; tuberculosis; lung; macrophage; innate immunity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Pyle, C.J.; Azad, A.K.; Papp, A.C.; Sadee, W.; Knoell, D.L.; Schlesinger, L.S. Elemental Ingredients in the Macrophage Cocktail: Role of ZIP8 in Host Response to Mycobacterium tuberculosis. Int. J. Mol. Sci. 2017, 18, 2375.

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