The iron export protein ferroportin 1 is differentially expressed in mouse macrophage populations and is present in the mycobacterial-containing phagosome.
Intracellular pathogens, including Mycobacterium tuberculosis, obtain iron from the host for their survival. Ferroportin 1 (FPN1; SLC40A1) is the sole iron exporter from mammalian cells and is expressed in the duodenum and macrophages. In the present study, we show that FPN1 mRNA levels in the mouse macrophage cell line RAW264.7 are synergistically induced by treatment with live or gamma-irradiated M. tuberculosis and IFN-gamma. FPN1 mRNA levels were also induced by Mycobacterium avium and IFN-gamma in RAW264.7 cells and the mouse alveolar macrophage cell line AMJ2-C8. Treatment of mouse resident peritoneal macrophages with M. tuberculosis and IFN-gamma resulted in a sixfold increase in FPN1 mRNA expression. In contrast, M. tuberculosis and IFN-gamma inhibited FPN1 mRNA expression in bone marrow-derived macrophages and lung macrophages, which have high basal levels of FPN1 mRNA expression. Using confocal microscopy, FPN1 protein localized rapidly to M. tuberculosis phagosomes after infection in RAW264.7 macrophages. In RAW264.7 cells expressing wild-type natural resistance-associated macrophage protein 1 (Nramp1(Gly169)), FPN1 and Nramp1 partially colocalized in late endosomes/lysosomes prior to infection. After 2 h of infection, Nramp1 and FPN1 were present in M. tuberculosis phagosomes. Our studies provide evidence for transcriptional regulation of FPN1 by pathogenic mycobacteria and IFN-gamma, which is dependent on the macrophage type. The trafficking of FPN1 to the M. tuberculosis phagosome suggests that it is involved in regulating iron availability to the mycobacteria in this locale.
Van Zandt
Kristopher E
KE
Department of Microbiology, The Ohio State University, 333 W. 10th Ave., Columbus, OH 43210, USA.
Sow
Fatoumata B
FB
Florence
William C
WC
Zwilling
Bruce S
BS
Satoskar
Abhay R
AR
Schlesinger
Larry S
LS
Lafuse
William P
WP
D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009162:Mycobacterium avium / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000098742:Ferroportin; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D007371:Interferon-gamma; D007501:Iron; D000098742:Ferroportin; D000099173:Natural Resistance-associated Macrophage Protein 1