Contribution of Renal Tubule Epithelial Cells in the Innate Immune Response during Renal Bacterial Infections and Ischemia-reperfusion Injury

The epithelial cells that line the renal tubule are sometimesseverely injured in the course of inflammatory kidneydiseases. These renal tubule epithelial cells (RTECs) expresssome of the Toll-like receptors (TLRs) of the innate immunesystem. A number of studies have implicated RTECs, togetherwith bone marrow-derived cells, in triggering an innateimmune response to bacterial infection and/or ischemic stress.RTECs expressing TLR4, which recognizes lipopolysaccharide(LPS), contribute to defending the host against ascending urinarytract infections (UTIs) caused by uropathogenicEscherichia coli (UPECs). Activation of TLR2 and TLR4 signalingby endogenous damage-associated molecular patternscontrols the inflammatory responses of RTECs and cell apoptosisin kidneys subjected to ischemia/reperfusion (I/R) injury.This review will consider some recent advances in understandingof the role of RTECs in inducing the innate immune response in experimental models ofascending UTIs and renal I/R injury. Arginine vasopressin, which regulates renal waterabsorption, has been shown to act as a potent modulator of the innate response in collectingduct cells, a preferred intrarenal site for UPEC adhesion. The activation of the mitogen-associatedprotein kinase ERK1/2 in post-hypoxic RTECs has also been shown to be selectivelyregulated by TLR2 via the serine-threonine protein phosphatase 5, which is associated withthe endoplasmic reticulum resident heat shock protein, gp96, which acts as a master chaperoneof TLRs. These findings provide further support for the concept that RTECs are activelyinvolved in triggering the innate immune response, at least in the context of ascending UTIsand I/R injury