Iron overload promotes rapid growth and dissemination of Y enterocolitica O9. (A) Survival of naturally iron-loaded or dietary iron-depleted HKO mice after IP infection with 108 CFU Y enterocolitica O9 is comparable to that after oral infection (Figure 1C) indicating that intestinal bacterial translocation is not the critical iron-dependent step. (B-H) Iron-loaded or iron-depleted (depl) HKO mice were orally infected with 108 CFUs per mouse Y enterocolitica O9. (B-C) Liver and serum iron concentrations confirmed iron loading and iron depletion of HKO mice. (D) Iron-loaded HKOs had dramatically increased bacterial dissemination to the liver, spleen, and blood as assessed by tissue CFUs, and consequently (E) much higher liver Saa1 mRNA expression compared with iron-depleted HKOs. (F-H) Hematoxylin and eosin (H&E) and staining with antibody (Ab) specific for Y enterocolitica O9 of tissue sections from the liver, spleen, and Peyer patches of iron-loaded (in green rectangles) or iron-depleted (in blue rectangles) HKO mice; ×10 magnification. Arrows point to bacterial abscesses. Survival is defined in “Methods.” Statistical analysis of survival curves (A) was performed using multifactorial Kaplan-Meier log-rank analysis. Statistical analysis in panels B through E was performed using the Student t test for normally distributed data (D: spleen CFUs; E) and the Mann-Whitney U test for data that were not normally distributed. ΔCt, Δcycle threshold; hprt, hypoxanthine-guanine phosphoribosyltransferase.
