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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3727-3732. Prepublished online as a Blood First Edition Paper on January 3, 2006; DOI 10.1182/blood-2005-06-2259. This Article Full Text (PDF) All Versions of this Article: 2005-06-2259v1 107/9/3727    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Peyssonnaux, C. Articles by Nizet, V. Search for Related Content PubMed PubMed Citation Articles by Peyssonnaux, C. Articles by Nizet, V. Social Bookmarking                   What's this? Next Article  Submitted June 6, 2005 Accepted December 25, 2005 TLR-4 dependent hepcidin expression by myeloid cells in response to bacterial pathogens Carole Peyssonnaux, Annelies S Zinkernagel, Vivekanand Datta, Xavier Lauth, Randall S Johnson, and Victor Nizet* Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA Kent SeaTech Corporation, San Diego, CA, USA Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA * Corresponding author; email: vnizet{at}ucsd.edu. Hepcidin is an antimicrobial peptide secreted by the liver during inflammation that plays a central role in mammalian iron homeostasis. Here we demonstrate the endogenous expression of hepcidin by macrophages and neutrophils in vitro and in vivo. These myeloid cell types produced hepcidin in response to bacterial pathogens in a TLR-4 dependent fashion. Conversely, bacterial stimulation of macrophages triggered a TLR-4 dependent reduction in the iron exporter ferroportin. In vivo, intraperitoneal challenge with Pseudomonas aeruginosa induced TLR-4 dependent hepcidin expression and iron deposition in splenic macrophages, findings mirrored in subcutaneous infection with group A Streptococcus where hepcidin induction was further observed in neutrophils migrating to the tissue site of infection. Hepcidin expression in cultured hepatocytes or in the livers of mice infected with bacteria was independent of TLR4, suggesting the TLR4-hepcidin pathway is restricted to myeloid cells types. Our findings identify endogenous myeloid cell hepcidin production as a previously unrecognized component of the host response to bacterial pathogens. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Matsui, Y. Sekiya, M. Nakamura, S. Y. Murayama, H. Yoshida, T. Takahashi, K. Imanishi, K. Tsuchimoto, T. Uchiyama, K. Sunakawa, et al. CD46 Transgenic Mouse Model of Necrotizing Fasciitis Caused by Streptococcus pyogenes Infection Infect. Immun., November 1, 2009; 77(11): 4806 - 4814. [Abstract] [Full Text] [PDF] F. B. Sow, G. R. Alvarez, R. P. Gross, A. R. Satoskar, L. S. Schlesinger, B. S. Zwilling, and W. P. Lafuse Role of STAT1, NF-{kappa}B, and C/EBP{beta} in the macrophage transcriptional regulation of hepcidin by mycobacterial infection and IFN-{gamma} J. Leukoc. Biol., November 1, 2009; 86(5): 1247 - 1258. [Abstract] [Full Text] [PDF] C. L. Koening, J. C. Miller, J. M. Nelson, D. M. Ward, J. P. Kushner, L. K. Bockenstedt, J. J. Weis, J. Kaplan, and I. De Domenico Toll-like receptors mediate induction of hepcidin in mice infected with Borrelia burgdorferi Blood, August 27, 2009; 114(9): 1913 - 1918. 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