copper at the front line of the host-pathogen battle铜宿主-病原体战斗的前线.pdfVIP

Pearls Copper at the Front Line of the Host-Pathogen Battle Richard A. Festa, Dennis J. Thiele* Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of America Introduction with infectious Mycobacterium species, there is a time-dependent accumulation of Cu within the phagosome [5]. Recent work in the Copper (Cu) is a transition metal used by life from bacteria to Petris laboratory has shown, in both macrophage-like cell lines and eukaryotes in many cellular processes as a biochemical cofactor in primary macrophages, that levels of the Ctr1 Cu+ importer are and a signaling molecule. However, while Cu plays critical cellular elevated in IFN-c and LPS-activated macrophages [6]. Further- roles, it can be toxic when allowed to accumulate to levels well more, the steady state protein levels of the ATP7A Cu pump, beyond cellular needs. This razor’s edge between the essentiality which delivers Cu to the secretory compartment or exports Cu and toxicity of Cu is emerging as a critical host defense mechanism from most cell types, is elevated and ATP7A is partially localized at the heart of the host-pathogen axis. Accumulating evidence to the phagolysosome, suggesting that the phagolysosomal suggests that the innate immune response commandeers the toxic accumulation of Cu is due to the recruitment of these two Cu properties of Cu to attack invading infectious organisms, while transporters (Figure 1). Consistent with these observations, E. coli pathogenic bacteria and fungi have implemented robust