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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2017 Nov 10

PMID 29120360

Citations 15

Authors

Charlie J Pyle

Abul K Azad

Audrey C Papp

Wolfgang Sadee

Daren L Knoell

Larry S Schlesinger

Affiliations

Soon will be listed here.

Abstract

Tuberculosis (TB) is a global epidemic caused by the infection of human macrophages with the world's most deadly single bacterial pathogen, (). 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 infection of macrophages, and we have observed its localization to the 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 , it is not yet clear whether ZIP-guided zinc transport serves as a host protective factor or, rather, is targeted by to enable its phagosomal survival.

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