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

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.

Flagellin/TLR5 signalling activates renal collecting duct cells and facilitates invasion and cellular translocation of uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPEC) colonizing kidneys is the main cause of acute pyelonephritis. TLR5 that senses flagellin was shown to be highly expressed in the bladder and to participate in host defence against flagellated UPEC, although its role in kidneys still remains elusive. Here we show that TLR5 is expressed in renal medullary collecting duct (MCD) cells, which represent a preferential site of UPEC adhesion.

Calcineurin/NFAT signaling and innate host defence: a role for NOD1-mediated phagocytic functions.

The calcineurin/nuclear factor of activated T cells (NFATs) signaling pathway plays a central role in T cell mediated adaptive immune responses, but a number of recent studies demonstrated that calcineurin/NFAT signaling also plays a key role in the control of the innate immune response by myeloid cells. Calcineurin inhibitors, such as cyclosporine A (CsA) and tacrolimus (FK506), are commonly used in organ transplantation to prevent graft rejection and in a variety of immune diseases. These immunosuppressive drugs have adverse effects and significantly increase host's susceptibility towards bacterial or fungal infections.

Neonatal immune adaptation of the gut and its role during infections.

The intestinal tract is engaged in a relationship with a dense and complex microbial ecosystem, the microbiota. The establishment of this symbiosis is essential for host physiology, metabolism, and immune homeostasis. Because newborns are essentially sterile, the first exposure to microorganisms and environmental endotoxins during the neonatal period is followed by a crucial sequence of active events leading to immune tolerance and homeostasis.

Cyclosporine A impairs nucleotide binding oligomerization domain (Nod1)-mediated innate antibacterial renal defenses in mice and human transplant recipients.

Acute pyelonephritis (APN), which is mainly caused by uropathogenic Escherichia coli (UPEC), is the most common bacterial complication in renal transplant recipients receiving immunosuppressive treatment. However, it remains unclear how immunosuppressive drugs, such as the calcineurin inhibitor cyclosporine A (CsA), decrease renal resistance to UPEC. Here, we investigated the effects of CsA in host defense against UPEC in an experimental model of APN.