title: Mycobacterium tuberculosis components stimulate production of the antimicrobial peptide hepcidin.
abstract: We investigated the in vitro production of the antimicrobial peptide hepcidin by cells of the innate immune system that harbor Mycobacterium tuberculosis. Stimulation of mouse lung macrophages with M. tuberculosis or IFN-γ + M. tuberculosis induced hepcidin mRNA. In human alveolar A549 epithelial cells, lipoglycans of M. tuberculosis, in particular mannose-capped lipoarabinomannan and phosphatidyl-myo-inositol mannosides, were strong inducers of hepcidin mRNA. In mouse dendritic cells, hepcidin mRNA was increased by subcellular fractions and culture filtrate proteins of M. tuberculosis and by TLR2 and TLR4 agonists, but not by TLR9 agonists, IL-1α, IL-6 or TNF-α. Flow cytometry evaluation of human peripheral blood mononuclear cells demonstrated that CD11c(+) myeloid dendritic cells stimulated with killed M. tuberculosis or live M. bovis BCG produced hepcidin. The production of the antimicrobial peptide hepcidin by cells that interact with M. tuberculosis suggests a host defense mechanism against mycobacteria.
authors.affiliation: Division of TB Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta GA 30333, USA. sow.4@osu.edu
authors.forename: Fatoumata B
authors.initials: FB
authors.lastname: Sow
authors.forename: Subhadra
authors.initials: S
authors.lastname: Nandakumar
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Velu
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Kellar
authors.forename: Larry S
authors.initials: LS
authors.lastname: Schlesinger
authors.forename: Rama R
authors.initials: RR
authors.lastname: Amara
authors.forename: William P
authors.initials: WP
authors.lastname: Lafuse
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Shinnick
authors.forename: Suraj B
authors.initials: SB
authors.lastname: Sable
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D064451:Hepcidins; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D012333:RNA, Messenger / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists; D051197:Toll-Like Receptor 4 / Q000819:agonists; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D007371:Interferon-gamma