Hepatocytes: a key cell type for innate immunity

Abstract

Hepatocytes, the major parenchymal cells in the liver, play pivotal roles in metabolism, detoxification, and protein synthesis. Hepatocytes also activate innate immunity against invading microorganisms by secreting innate immunity proteins. These proteins include bactericidal proteins that directly kill bacteria, opsonins that assist in the phagocytosis of foreign bacteria, iron-sequestering proteins that block iron uptake by bacteria, several soluble factors that regulate lipopolysaccharide signaling, and the coagulation factor fibrinogen that activates innate immunity. In this review, we summarize the wide variety of innate immunity proteins produced by hepatocytes and discuss liver-enriched transcription factors (e.g. hepatocyte nuclear factors and CCAAT/enhancer-binding proteins), pro-inflammatory mediators (e.g. interleukin (IL)-6, IL-22, IL-1β and tumor necrosis factor-α), and downstream signaling pathways (e.g. signal transducer and activator of transcription factor 3 and nuclear factor-κB) that regulate the expression of these innate immunity proteins. We also briefly discuss the dysregulation of these innate immunity proteins in chronic liver disease, which may contribute to an increased susceptibility to bacterial infection in patients with cirrhosis.

Figure 1

Critical roles of hepatocytes in anti-bacterial innate immunity. Upon bacterial infection, immune cells secrete cytokines to stimulate hepatocytes to produce anti-bacterial proteins. The pro-inflammatory cytokines activate the transcription factors NF-κB and STAT3. Along with liver-enriched transcription factors HNFs and C/EBPs, they promote the expression of many anti-bacterial proteins as listed. These proteins eliminate the bacteria and orchestrate the innate immune function.