期刊
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 27, 期 3, 页码 835-846出版社
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2014101035
关键词
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资金
- INSERM
- Universite Paris Diderot, France
- program 'University of Sorbonne Paris Cite, Excellence Initiative, IDEX', reference KIRON
- Universite Paris Diderot
- Societe Francaise d'Hematologie
- Laboratory of excellence, GR-Ex, Paris, France
- program 'Investissements d'avenir' of the French National Research Agency [ANR-11-LABX-0051, ANR-11-IDEX-0005-02]
- Fondation pour la Recherche Medicale Francaise
The iron-regulatory peptide hepcidin exhibits antimicrobial activity. Having previously shown hepcidin expression in the kidney, we addressed its role in urinary tract infection (UTI), which remains largely unknown. Experimental UTI was induced in wild-type (WT) and hepcidin-knockout (Hepc-/-) mice using the uropathogenic Escherichia coli CFT073 strain. Compared with infected WT mice, infected Hepc-/- mice showed a dramatic increase in renal bacterial load. Moreover, bacterial invasion was significantly dampened by the pretreatment of WT mice with hepcidin. Infected Hepc-/- mice exhibited decreased iron accumulation in the renal medulla and significant attenuation of the renal inflammatory response. Notably, we demonstrated in vitro bacteriostatic activity of hepcidin against CFT073. Furthermore, CFT073 repressed renal hepcidin, both in vivo and in cultured renal cells, and reduced phosphorylation of SMAD kinase in vivo, suggesting a bacterial strategy to escape the antimicrobial activities of hepcidin. In conclusion, we provide new mechanisms by which hepcidin contributes to renal host defense and suggest that targeting hepcidin offers a strategy to prevent bacterial invasion.
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