Premium
Mycobacteria, metals, and the macrophage
Author(s) -
Neyrolles Olivier,
Wolschendorf Frank,
Mitra Avishek,
Niederweis Michael
Publication year - 2015
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12265
Subject(s) - phagosome , mycobacterium tuberculosis , tuberculosis , biology , microbiology and biotechnology , macrophage , immune system , intracellular parasite , immunity , immunology , phagocytosis , medicine , genetics , pathology , in vitro
Summary Mycobacterium tuberculosis is a facultative intracellular pathogen that thrives inside host macrophages. A key trait of M. tuberculosis is to exploit and manipulate metal cation trafficking inside infected macrophages to ensure survival and replication inside the phagosome. Here, we describe the recent fascinating discoveries that the mammalian immune system responds to infections with M. tuberculosis by overloading the phagosome with copper and zinc, two metals which are essential nutrients in small quantities but are toxic in excess. M. tuberculosis has developed multi‐faceted resistance mechanisms to protect itself from metal toxicity including control of uptake, sequestration inside the cell, oxidation, and efflux. The host response to infections combines this metal poisoning strategy with nutritional immunity mechanisms that deprive M. tuberculosis from metals such as iron and manganese to prevent bacterial replication. Both immune mechanisms rely on the translocation of metal transporter proteins to the phagosomal membrane during the maturation process of the phagosome. This review summarizes these recent findings and discusses how metal‐targeted approaches might complement existing TB chemotherapeutic regimens with novel anti‐infective therapies.