Journal
BIOCHEMICAL JOURNAL
Volume 444, Issue -, Pages 51-57Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20112180
Keywords
copper redistribution; copper sensor 1 (CS 1); innate immunity; macrophage; Salmonella
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Funding
- National Health and Medical Research Council (NHMRC), Australia [519722, APP1003470]
- Australian Research Council (ARS) [DP1096029]
- ARC [FT100100662, FT100100657]
- University of Queensland
- Australian Cancer Research Foundation (ACRF)
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The movement of key transition metal ions is recognized to be of critical importance in the interaction between macrophages and intracellular pathogens. The present study investigated the role of copper in mouse macrophage responses to Salmonella enterica sv. Typhimurium. The copper chelator BCS (bathocuproinedisulfonic acid, disodium salt) increased intracellular survival of S. Typhimurium within primary mouse BMM (bone-marrow-derived macrophages) at 24 h post-infection, implying that copper contributed to effective host defence against this pathogen. Infection of BMM with S. Typhimurium or treatment with the TLR (Toll-like receptor) 4 ligand LPS (lipopolysaccharide) induced the expression of several genes encoding proteins involved in copper transport [Ctr (copper transporter) I, Ctr2 and Atp7a (copper-transporting ATPase I)], as well as the multi-copper oxidase Cp (caeruloplasmin). Both LPS and infection with S. Typhirnurium triggered copper accumulation within punctate intracellular vesicles (copper 'hot spots') in BMM as indicated by the fluorescent reporter CS 1 (copper sensor 1). These copper hot spots peaked in their accumulation at approximately 18 h post-stimulation and were dependent on copper uptake into cells. Localization studies indicated that the copper hot spots were in discrete vesicles distinct from Salmonella containing vacuoles and lysosomes. We propose that copper hot spot formation contributes to antimicrobial responses against professional intracellular bacterial pathogens.
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