title: Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient mice.
abstract: Mycobacterium avium is an opportunistic infectious agent in immunocompromised patients, living inside macrophage phagosomes. As for other mycobacterial species, iron availability is a critical factor for M. avium survival and multiplication. Indeed, an association between host secondary iron overload and increased susceptibility to these mycobacteria is generally acknowledged. However, studies on the impact of primary iron overload on M. avium infection have not been performed. In this work, we used animal models of primary iron overload that mimic the human disease hereditary hemochromatosis. This pathology is characterized by increased serum transferrin saturation with iron deposition in parenchymal cells, mainly in the liver, and is most often associated with mutations in the gene encoding the molecule HFE. In this paper, we demonstrate that mice of two genetically determined primary iron overload phenotypes, Hfe(-/-) and beta2m(-/-), show an increased susceptibility to experimental infection with M. avium and that during infection these animals accumulate iron inside granuloma macrophages. beta2m(-/-) mice were found to be more susceptible than Hfe(-/-) mice, but depleting Hfe(-/-) mice of CD8(+) cells had no effect on resistance to infection. Overall, our results suggest that serum iron, rather than total liver iron, levels have a considerable impact on susceptibility to M. avium infection.
authors.affiliation: Laboratory of Microbiology and Immunology of Infection, Iron Genes and the Immune System, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal. sgomes@ibmc.up.pt
authors.forename: Sandra
authors.initials: S
authors.lastname: Gomes-Pereira
authors.forename: Pedro Nuno
authors.initials: PN
authors.lastname: Rodrigues
authors.forename: Rui
authors.initials: R
authors.lastname: Appelberg
authors.forename: Maria Salomé
authors.initials: MS
authors.lastname: Gomes
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015169:Colony Count, Microbial; D004198:Disease Susceptibility; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000737:chemistry; D008565:Membrane Proteins / Q000172:deficiency* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009162:Mycobacterium avium / Q000276:immunology*; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D001613:beta 2-Microglobulin / Q000172:deficiency
chemical_list: D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D001613:beta 2-Microglobulin; D007501:Iron