Cyclosporine A Induces MicroRNAs Controlling Innate Immunity during Renal Bacterial Infection.
J Innate Immun
; 10(1): 14-29, 2018.
Article
em En
| MEDLINE
| ID: mdl-29069656
ABSTRACT
Urinary tract infections (UTIs) mainly due to uropathogenic Escherichia coli (UPEC) are one of the most frequent complications in kidney-transplanted patients, causing significant morbidity. However, the mechanisms underlying UTI in renal grafts remain poorly understood. Here, we analysed the effects of the potent immunosuppressive agent cyclosporine A (CsA) on the activation of collecting duct cells that represent a preferential site of adhesion and translocation for UPEC. CsA induced the inhibition of lipopolysaccharide- induced activation of collecting duct cells due to the downregulation of the expression of TLR4 via the microRNA Let-7i. Using an experimental model of ascending UTI, we showed that the pretreatment of mice with CsA prior to infection induced a marked fall in cytokine production by collecting duct cells, neutrophil recruitment, and a dramatic rise of bacterial load, but not in infected TLR4-defective mice kidneys. This effect was also observed in CsA-treated infected kidneys, where the expression of Let-7i was increased. Treatment with a synthetic Let-7i mimic reproduced the effects of CsA. Conversely, pretreatment with an anti-Let-7i antagonised the effects of CsA and rescued the innate immune response of collecting duct cells against UPEC. Thus, the utilisation of an anti-Let-7i during kidney transplantation may protect CsA-treated patients from ascending bacterial infection.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções Urinárias
/
Ciclosporina
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MicroRNAs
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Infecções por Escherichia coli
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Escherichia coli Uropatogênica
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Imunossupressores
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Túbulos Renais Coletores
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Innate Immun
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
França