Immune cell phenotype and function in different compartments of the gut-liver-axis in chronic liver disease

Abstract

Abstract BACKGROUND The liver is exposed to gut-derived products via the portal vein and bacterial translocation is associated with chronic liver disease. Here we analyzed immune cell activation and function in three compartments of the gut-liver axis: systemic blood, portal vein blood and liver. METHODS Natural killer (NK) cells, mucosal associated invariant T (MAIT) cells and conventional CD8 T cells were studied in liver and blood of 29 patients with chronic hepatitis C prior to and after Sofosbuvir/Velpatasvir-induced viral clearance. RESULTS NK, MAIT and conventional CD8 T cells were more activated (CD69+, HLA-DR+) and more cytotoxic (CD107a+) in the liver than in systemic and portal blood. Monocytes were also more activated in the liver and plasma levels of monocyte-derived IL-18 correlated with liver inflammation. Consistent with the activation of intrahepatic immune cells, levels of sCD14, sCD163 and sCD27 were higher in systemic than in portal plasma. However, immune cell activation and degranulation were not different in systemic and portal vein blood. Likewise, the in vitro functional responses of monocytes to lipopolysaccharide and of MAIT cells to riboflavin-synthesizing bacteria did not differ between systemic and portal blood. Intrahepatic immune cell activation declined rapidly within four weeks of antiviral therapy and remained stable for up to 36 weeks post treatment. CONCLUSIONS Immune cell activation and inflammation are compartmentalized to the liver in patients with compensated HCV-related liver disease. Plasma markers of immune cell activation are higher in systemic than in portal plasma. The rapid decline of intrahepatic immune cell activation suggests that it is primarily driven by viral infection.