Abstract:
:Withdrawal of iron from serum (hypoferraemia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient from invading pathogens, impairing their growth. Hepcidin (Hamp1) is the master regulator of iron and its expression is induced by inflammation. Mice lacking Hamp1 from birth rapidly accumulate iron and are susceptible to infection by blood-dwelling siderophilic bacteria such as Vibrio vulnificus. In order to study the innate immune role of hepcidin against a background of normal iron status, we developed a transgenic mouse model of tamoxifen-sensitive conditional Hamp1 deletion (termed iHamp1-KO mice). These mice attain adulthood with an iron status indistinguishable from littermate controls. Hamp1 disruption and the consequent decline of serum hepcidin concentrations occurred within hours of a single tamoxifen dose. We found that the TLR ligands LPS and Pam3CSK4 and heat-killed Brucella abortus caused an equivalent induction of inflammation in control and iHamp1-KO mice. Pam3CSK4 and B. abortus only caused a drop in serum iron in control mice, while hypoferraemia due to LPS was evident but substantially blunted in iHamp1-KO mice. Our results characterise a powerful new model of rapidly inducible hepcidin disruption, and demonstrate the critical contribution of hepcidin to the hypoferraemia of inflammation.
journal_name
J Innate Immunjournal_title
Journal of innate immunityauthors
Armitage AE,Lim PJ,Frost JN,Pasricha SR,Soilleux EJ,Evans E,Morovat A,Santos A,Diaz R,Biggs D,Davies B,Gileadi U,Robbins PA,Lakhal-Littleton S,Drakesmith Hdoi
10.1159/000447713subject
Has Abstractpub_date
2016-01-01 00:00:00pages
517-28issue
5eissn
1662-811Xissn
1662-8128pii
000447713journal_volume
8pub_type
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pub_type: 杂志文章
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journal_title:Journal of innate immunity
pub_type: 杂志文章
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journal_title:Journal of innate immunity
pub_type: 杂志文章
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journal_title:Journal of innate immunity
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journal_title:Journal of innate immunity
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journal_title:Journal of innate immunity
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journal_title:Journal of innate immunity
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journal_title:Journal of innate immunity
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journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
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更新日期:2011-01-01 00:00:00
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journal_title:Journal of innate immunity
pub_type: 杂志文章
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更新日期:2013-01-01 00:00:00
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journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000509715
更新日期:2020-01-01 00:00:00
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journal_title:Journal of innate immunity
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更新日期:2009-01-01 00:00:00
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pub_type: 杂志文章,评审
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