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Hepcidin as a Major Component of Renal Antibacterial Defenses against
Uropathogenic Escherichia coli
#MMPMID26293821
Houamel D
; Ducrot N
; Lefebvre T
; Daher R
; Moulouel B
; Sari MA
; Letteron P
; Lyoumi S
; Millot S
; Tourret J
; Bouvet O
; Vaulont S
; Vandewalle A
; Denamur E
; Puy H
; Beaumont C
; Gouya L
; Karim Z
J Am Soc Nephrol
2016[Mar]; 27
(3
): 835-46
PMID26293821
show ga
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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