Toll-like receptors and danger signaling in kidney injury.

Abstract

Why does renal inflammation appear among many of the so-called noninflammatory kidney diseases? Toll-like receptor research provides a surprising answer because activation of the innate immune system involves pathogen-derived as well as nonpathogen-derived immunostimulatory molecules; thus, metabolic, hemodynamic, toxic, or autoimmune forms of tissue damage all can trigger an innate inflammatory response. Because receptor activation is unable to eliminate the underlying drivers of these nonpathogen diseases, it becomes instead a maladaptive pathogenic mechanism that aggravates renal damage. Genetic variants in danger-signaling genes of the innate immune system can also affect individual risk for insufficient pathogen control or exaggerated nonpathogen-related tissue pathology. The evolving concept of danger signaling provides a general mechanism for kidney injury.