Systemic candidiasis perturbs copper homeostatic functions in the liver and spleen.

<p>Progressive <i>C</i>. <i>albicans</i> infection affects the expression of copper homeostatic functions in the liver at transcript (A) and protein (B) levels. As the infection progresses, the abundance of hepatic transcripts for the metal storage protein metallothionein MT1 and the copper-containing ferroxidase ceruloplasmin (CP) increase, while the abundance of the copper importer <i>Ctr1</i> transcript decreases (A). In contrast, hepatic ceruloplasmin protein levels do not increase with progressive <i>C</i>. <i>albicans</i> infection, while CTR1 protein levels diminish (B), as assessed by immunohistochemistry (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0158683#sec002" target="_blank">Materials and Methods</a>). All transcript data were acquired in duplicate from four biological replicates: healthy mice (replicates H1–H4), animals at early (24 h, replicates E1–E4) or late (96 h, replicates L1–L4) infection stages, following injection with saline (controls, H) or <i>C</i>. <i>albicans</i> SC5314. Transcript abundances were normalised against the <i>GAPDH</i> mRNA. Fold differences in expression are given when <i>p</i>≤0.05. Numerical data are provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0158683#pone.0158683.s008" target="_blank">S4 Table</a>. (C) In the spleen, the red pulp macrophage population remains relatively constant, as revealed by detection of the red pulp macrophage antigen F4/80. The haem oxygenase HO-1, CTR1 importer and trans-Golgi ATPase ATP7B all decrease in the red pulp over the course of infection. Images are representative of four biological replicates. Brown colour indicates positive reaction and blue colour no reaction. Size bars: 5 mm (B) or 200 μm (C).