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The innate immune system is our first line of defense against infection and injury, and responsible for initiating inflammatory and immune responses to resolve infections and repair injured tissues. This review focuses on the Toll-like receptors (TLRs) of the innate immune system and their role in recognizing infection and injury, and regulating inflammatory responses in the kidney.There is increasing data to support a role for TLRs in immune complex-mediated glomerulonephritis. TLR7 has emerged as a key regulator of autoantibody production in murine lupus nephritis. In addition, studies have implicated TLR recognition of endogenous molecules released during cellular necrosis as critical regulators of sterile inflammation and injury. Tonic interactions between TLRs and environmental agonists derived from commensal microbes and endogenous sources may also influence autoimmune disease and inflammatory disorders affecting the kidney.Future studies to decipher the contribution of TLRs and other innate immune receptors in the regulation of inflammation, immune responses, and injury in the kidney will pave the way for novel therapeutic interventions.