Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
Int J Mol Sci. 2017 Nov 9;18(11):2375. doi: 10.3390/ijms18112375.
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.
结核病（TB）是一种全球性的传染病，由人类巨噬细胞感染世界上最致命的单一细菌病原体引起（）。它存在于巨噬细胞的吞噬小体中，微量元素浓度影响免疫反应、细菌金属代谢和细菌存活。微量元素的操纵是宿主防御感染的关键机制。特别是人类锌转运蛋白 Zrt-/Irt 样蛋白 8（ZIP8），是 14 个 ZIP 家族成员之一，在包括锌在内的二价阳离子流入巨噬细胞质的过程中很重要。也观察到它存在于细胞细胞器的膜上，在那里它可以作为一种外排泵，将锌转运到细胞质中。ZIP8 可被巨噬细胞感染强烈诱导，我们观察到它定位于 吞噬体。ZIP8 和其他二价阳离子转运蛋白在巨噬细胞中的表达、定位和功能对结核病的预防和传播有重要意义，值得进一步研究。特别是，考虑到锌作为人类和所必需的必需营养素的重要性，目前尚不清楚 ZIP 指导的锌转运是作为宿主保护因子起作用，还是被 靶向以使其吞噬体存活。
