%0 Generic %A M., Sadio %A E., Tourneur %A M., Bens %A J.-M., Goujon %A A., Vandewalle %A C., Chassin %D 2017 %T Supplementary Material for: Cyclosporine A Induces MicroRNAs Controlling Innate Immunity during Renal Bacterial Infection %U https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Cyclosporine_A_Induces_MicroRNAs_Controlling_Innate_Immunity_during_Renal_Bacterial_Infection/5537506 %R 10.6084/m9.figshare.5537506.v1 %2 https://karger.figshare.com/ndownloader/files/9586666 %2 https://karger.figshare.com/ndownloader/files/9586669 %2 https://karger.figshare.com/ndownloader/files/9586675 %2 https://karger.figshare.com/ndownloader/files/9586672 %2 https://karger.figshare.com/ndownloader/files/9586678 %2 https://karger.figshare.com/ndownloader/files/9586681 %K Collecting duct %K Escherichia coli %K Toll-like receptor 4 %K Let-7i %K Kidney %X

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.

%I Karger Publishers