Multifaceted roles of Toll-like receptors in acute kidney injury

Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) in the first line defense system of our bodies; they are widely expressed on leukocytes and kidney epithelial cells. Infections due to pathogens or danger signals from injured tissues often activate several TLRs and these receptors mediate their signal transduction through the activation of transcription factors that regulate the expression of cytokine interleukin-1β (IL-1β), type I interferons (IFNs), and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) dependent cytokines and chemokines. Acute kidney injury (AKI) involves early Toll-like receptors driven immunopathology, while resolution of inflammation is needed for rapid regeneration of injured tubular cells. Despite their well known function in the progression of inflammation; interestingly, activation of TLRs also has been implicated in renal epithelial repair through the induction of certain interleukins and improvement in autophagy mechanism. Studies have found that although the blockade of TLRs during the early injury phase of renal tissues prevented tubular necrosis, suppression of interleukins production and impaired kidney regeneration due to their blockade has been observed during the healing phase of tissue. Taken together, these results suggest that the two danger response programs of renal cells i.e. renal inflammation and regeneration may link at the level of TLRs. This review aims to emphasize on the role of TLRs signaling in different acute kidney injury phases. Understanding of these pathways may turn out to be effective as therapeutic option for kidney diseases.