Innate immunity and the liver

Abstract

The liver contains a wide array of immune cells such as macrophages, dendritic cells, and lymphocytes. In addition, nonimmune liver cells participate in the immune system by producing soluble pattern recognition receptors (PRRs) and complement proteins. This liver-mediated immune system maintains the local defense against microbial infection as well as systemic homeostasis. In fact, patients with advanced liver diseases have a high risk for infection due to impaired biosynthesis of secreted PRRs. Thus, the liver is to be considered as an immune organ. The innate immune system can promptly eliminate nonspecific pathogens using several types of PRRs, including Toll-like receptors, NOD-like receptors, RIG-I-like receptors, and complement proteins. Representative products that act through PRR signaling are cytokines, which have antibacterial and antiviral effects. These mediators are used to kill pathogens with the assistance of other immune cells. Indeed, mice deficient in PRRs are susceptible to infection. However, an excessive immune response may lead to a sustained elevation of harmful cytokines. As a result, mice deficient in PRRs also show rather mild liver injuries, indicating that the lack of PRR signaling can provide beneficial effects. Thus, the innate immune system has dual functions in the prevention of infection as well as the development of liver diseases.