The liver as immune escape site for pathogens

Abstract

Besides its important function for protein, lipid and glucose metabolism the liver exerts scavenger function in order to clear the blood from degradation products. It is becoming increasingly clear that this scavenger function is closely linked to the liver’s immune function, which favours induction of immune tolerance rather than immunity. The cell population most actively involved in scavenging of blood-borne macromolecules is an organ-resident cell population, the liver sinusoidal endothelial cells (LSEC). LSEC also have prominent immune-regulatory function as they bear the capacity to prime naive CD4 and CD8 T-cells after presentation of exogenous antigens on MHC Class II or MHC Class I molecules, respectively. The outcome of such T-cell priming by antigen-presenting LSEC is induction of T-cell tolerance. Here, we also discuss the other mechanisms and cell populations involved in mediation of hepatic immune tolerance. We describe the mechanisms of how a virus may get across cell barriers, in particular the endothelial cell barrier. Importantly, blood-borne virus is scavenged by LSEC. Here we discuss the experimental evidence in the literature that virus uptake by LSEC does not necessarily lead to lysosomal destruction but rather results in transcytotic transport of the virus to hepatocytes. Thus, LSEC may play a pivotal role in hepatocellular infection by bloodborne virus: (i) retrieval from the bloodstream and transcytotic transport for infection of the target cell, the hepatocyte, and (ii) prevention of virus-specific CD8 T-cell immunity by skewing antigen-specific T-cell responses by presentation of viral antigens at the very early stage of infection.