Figure 4
Figure 4. Hepcidin induction by C albicans in vitro and in vivo. (A-B) Hepcidin and IL-6 induction in PBMCs after coculture with heat-killed C albicans. qRT-PCR measurement of fold-changes in (A) hepcidin and (B) IL-6 mRNA (relative to untreated controls from the same individual) in PBMCs (N = 3 donors, represented by different symbols) cultured for 22 hours in the presence of heat-killed C albicans yeast or hyphae (PBMC:Candida ratio = 5:1), with or without the Alk5/TGF-β1 pathway inhibitor, SD208 (1μM), and a mix of neutralizing anti–IL-6 and anti–IL6-R antibodies (10 μg/mL each, added 15 minutes before addition of C albicans or SD208 to cultures); goat IgG was used as an isotype control (20 μg/mL). Means are shown; P < .01, Friedman test; *P < .05 indicate Dunn multiple comparison test. (C-H) Hepcidin induction and effects on serum iron during acute systemic C albicans infection of mice. qRT-PCR measurement of (C) Hepcidin (Hamp1), (F) Id1, and (G) Fibrinogen α chain (Fga) mRNA expression relative to the endogenous control gene Hprt1 in livers of 8-week-old male C57BL/6 mice terminated 24 hours after intravenous infection with 5 × 105 C albicans strain SC5314 yeast cells (N = 8) or PBS (N = 4). Serum was taken at termination for calculation of (D) transferrin saturation. **P < .01, Mann-Whitney test. (E,H) Pearson correlation between (E) liver hepcidin mRNA and transferrin saturation, and between (H) liver hepcidin and Fga mRNA levels considering infected mice only.

Hepcidin induction by C albicans in vitro and in vivo. (A-B) Hepcidin and IL-6 induction in PBMCs after coculture with heat-killed C albicans. qRT-PCR measurement of fold-changes in (A) hepcidin and (B) IL-6 mRNA (relative to untreated controls from the same individual) in PBMCs (N = 3 donors, represented by different symbols) cultured for 22 hours in the presence of heat-killed C albicans yeast or hyphae (PBMC:Candida ratio = 5:1), with or without the Alk5/TGF-β1 pathway inhibitor, SD208 (1μM), and a mix of neutralizing anti–IL-6 and anti–IL6-R antibodies (10 μg/mL each, added 15 minutes before addition of C albicans or SD208 to cultures); goat IgG was used as an isotype control (20 μg/mL). Means are shown; P < .01, Friedman test; *P < .05 indicate Dunn multiple comparison test. (C-H) Hepcidin induction and effects on serum iron during acute systemic C albicans infection of mice. qRT-PCR measurement of (C) Hepcidin (Hamp1), (F) Id1, and (G) Fibrinogen α chain (Fga) mRNA expression relative to the endogenous control gene Hprt1 in livers of 8-week-old male C57BL/6 mice terminated 24 hours after intravenous infection with 5 × 105C albicans strain SC5314 yeast cells (N = 8) or PBS (N = 4). Serum was taken at termination for calculation of (D) transferrin saturation. **P < .01, Mann-Whitney test. (E,H) Pearson correlation between (E) liver hepcidin mRNA and transferrin saturation, and between (H) liver hepcidin and Fga mRNA levels considering infected mice only.

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