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Cell-specific role of Hfe in Salmonella infection
instance, H-Ft protein expression was lower in the spleen of Hfe-/- mice compared to Hfe+/+ littermates (Figure 5B). Furthermore, splenic Nos2 protein levels were higher in Hfe-/- and LysMCre+ Hfefl/fl mice and lower in AlfpCre+ Hfefl/fl mice as compared to their respective counterparts express- ing Hfe (Figure 5F). In addition, H-Ft (Online Supplementary Figure S4B) was higher and Tfr1 protein (Online Supplementary Figure S4C) was lower in both Hfe-/- mice and AlfpCre+ Hfefl/fl mice in comparison to the corresponding controls.
Hepatocyte-specific deletion of Hfe impairs cytokine formation
Finally, we aimed at better understanding why AlfpCre+ Hfefl/fl mice succumb to early death. Based on the result of organ-specific immune gene analyses (Tables 1 and 2), we assessed the levels of these circulating media- tors of immunity as well as markers of liver synthesis and damage: C3 is a complement factor produced by hepato- cytes and essential for the activation of the membrane attack complex which then destroys bacterial cell walls.
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Figure 3. Serum iron and hepcidin-1 levels are differentially affected by Hfe. Serum iron (A to C), hepcidin-1 (D and F) and Lcn2 (G to I) concen- trations of the mice infected for 72 hours were compared by Mann-Whitney test. n=9-12 for Hfe+/+, n=9-12 for Hfe-/-, 20 for AlfpCre– Hfefl/fl, n=11-13 for AlfpCre+ Hfefl/fl, n=10-15 for LysMCre– Hfefl/fl, n=10-15 for LysMCre+ Hfefl/fl.
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