Lcn2 is induced twofold in cells infected with Francisella (p = 0.01), but more than 15-fold when cells are infected

with Salmonella (p = 0.002). This might again Oligomycin A solubility dmso be expected because of the strong induction of the TLR-4 pathway by Salmonella in comparison to the preferred TLR-2 induction by Francisella. Salmonella, however, do not raise mRNA levels for the lipocalin receptor (LcnR), which are significantly increased in Francisella-infected macrophages (ABT-263 Figure 6A and 6B). Heme oxygenase (HO-1, Hmox1) catalyzes the conversion of heme to biliverdin, iron, and carbon monoxide. In macrophages it has an important antioxidative protective function, presumably by reducing pro-oxidant or pro-apoptotic hemoproteins [45, 46]. Not unexpectedly, the mRNA level for Hmox1 is increased in macrophages infected by Francisella and Salmonella (Figure 6A and 6B; p = 0.002 and p = 0.002 respectively). None of the components of the ferritin iron storage system are affected by infection with Salmonella or Francisella as measured by determining the expression of Fth1 and Ftl1 (Figure 6A and 6B; p = 0.91 and p = 0.90 for Francisella and p = 0.88 and p = 0.78 for Salmonella). These gene-expression data suggest that Francisella drives a more active transferrin-mediated

iron uptake program than Salmonella. Increased mRNA levels for IRP1 and IRP2 maintain increased selleck screening library translational levels for TfR1. Induction of genes required for transfer of iron to the cytosol Selleck Linsitinib via Dmt1 and Steap3 support the TfR1-mediated import route. Preferential induction of the TLR-4 pathway by Salmonella leads to a strong induction of hepcidin and lipocalin. We further sought to characterize the expression profile of these iron-homoestasis-related genes in the spiC and spiA Salmonella mutants, which lead to variable alterations in the LIP (Figure 5). Both mutant strains have a higher increase in the Steap3/DMT1 genes than wild-type Salmonella (p = 0.01 and

p = 0.001 for spiA Salmonella, and p = 0.01 and p = 0.003 for spiC Salmonella), while the induction of the iron-regulatory proteins IRP1 and IRP2 are lower (p = 0.02 for IRP1 and p = 0.02 for IRP2 in spiA Salmonella; p = 0.35 for IRP1 and p = 0.02 for IRP2 in spiC Salmonella). While TLR-4 driven induction of lipocalin is maintained in the mutant strains (p = 0.002 for spiA and p = 0.001 for spiC Salmonella), there is no induction of hepcidin (p = 0.89 and p = 0.78 respectively). The iron exporter Fpn1 is increased threefold in the spiC mutant (p = 0.01), while there is no increase in the spiA mutant (p = 0.78) (Figure 6C and 6D). This might be one possible explanation for the decrease in the labile iron pool in the spiC mutant in comparison to the spiA mutant (Figure 5).