Cell-specific expression of < i > Hfe < /i > determines the outcome of < i > Salmonella enterica < /i > serovar Typhimurium infection in mice.

Cell-specific expression of <i>Hfe</i> determines the outcome of <i>Salmonella enterica</i> serovar Typhimurium infection in mice. Haematologica. 2020 Oct 13;Online ahead of print: Authors: Nairz M, Metzendorf C, Vujic-Spasic M, Mitterstiller AM, Schroll A, Haschka D, Hoffmann A, Von Raffay L, Sparla R, Huck CW, Talasz H, Moser PL, Muckenthaler MU, Weiss G Abstract Mutations in HFE cause hereditary hemochromatosis type I hallmarked by increased iron absorption, iron accumulation in hepatocytes and iron deficiency in myeloid cells. HFE encodes an MHC-I like molecule, but its function in immune responses to infection remains incompletely understood. Here, we investigated putative roles of Hfe in myeloid cells and hepatocytes, separately, upon infection with Salmonella Typhimurium, an intracellular bacterium with iron-dependent virulence. We found that constitutive and macrophage-specific deletion of Hfe protected infected mice. The propagation of Salmonella in macrophages was reduced due to limited intramacrophage iron availability for bacterial growth and increased expression of the anti-microbial enzyme nitric oxide synthase-2. By contrast, mice with hepatocyte-specific deletion of Hfe succumbed earlier to Salmonella infection because of unrestricted extracellular bacterial replication associated with high iron availability in the serum and impaired expression of essential host defense molecules such as interl...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research