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Cyclosporine A Induces MicroRNAs Controlling Innate Immunity during Renal Bacterial Infection.

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.

SUBMITTER: Sadio M

PROVIDER: S-EPMC6757153 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Cyclosporine A Induces MicroRNAs Controlling Innate Immunity during Renal Bacterial Infection.

Sadio Malick M Tourneur Emilie E Bens Marcelle M Goujon Jean-Michel JM Vandewalle Alain A Chassin Cécilia C

Journal of innate immunity 20171026 1

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 inhib ...[more]

PMID: 29069656

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Cyclosporine A Induces MicroRNAs Controlling Innate Immunity during Renal Bacterial Infection.

Publications

Cyclosporine A Induces MicroRNAs Controlling Innate Immunity during Renal Bacterial Infection.

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