Premium
Role of Hepcidin in the Innate Immune Response to Mycobacterium tuberculosis
Author(s) -
Sow Fatoumata Ba,
Sable Suraj B,
Plikaytis Bonnie B,
Lafuse William P,
Shinnick Thomas M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.556
Subject(s) - hepcidin , innate immune system , proinflammatory cytokine , tlr2 , immune system , mycobacterium tuberculosis , immunology , tlr4 , biology , lipoarabinomannan , inflammation , microbiology and biotechnology , medicine , tuberculosis , pathology
In mammals, infection with the intracellular pathogen Mycobacterium tuberculosis results in the production of inflammatory cytokines and acute‐phase reactants in the liver, including the synthesis of the antimicrobial peptide hepcidin. Hepcidin controls extracellular iron by regulating its intestinal absorption and release from macrophages. Previously, we have shown that hepcidin is also induced in macrophages by the synergistic interaction of IFN‐γ and Mycobacterium tuberculosis infection. Here, we investigated the expression of hepcidin in the human lung epithelial cell line A549 and in mouse dendritic cells infected with M. tuberculosis H37Rv. We demonstrate that mycobacteria infection induced the expression of hepcidin mRNA and protein in the studied cells. Stimulation of A549 cells with IFN‐γ and the mycobacterial products lipoarabinomannan and phosphatidylinositol mannosides induced hepcidin mRNA expression. Similarly to macrophages, the proinflammatory cytokines IL1, IL6 and TNF‐α did not induce hepcidin in mouse dendritic cells. However, these cytokines significantly increased hepcidin mRNA induced by M. tuberculosis . We also show that hepcidin mRNA can be induced through TLR2, TLR4, and TLR9. The production of the antimicrobial peptide hepcidin by cells that are crucial to the generation of an effective immune response suggests a host defense mechanism to mycobacteria.