EFFECTOR FUNCTION OF HEPATOCYTES AND KUPFFER CELLS IN THE RESOLUTION OF SYSTEMIC BACTERIAL-INFECTIONS

It has been suggested that mononuclear phagocytes serve as the principal site of replication for a number of intracellular pathogens including Listeria monocytogenes. To determine the role of the tissue macrophages (Kupffer cells) in the proliferation of Listeria taken up in the liver, the hepatic cell populations were purified and the associated bacteria were quantified at periodic intervals postinfection. Here we report that the bulk of Listeria injected intravenously into nonimmune mice replicated within hepatocytes rather than Kupffer cells. Whereas a 200-fold increase in the number of hepatocyte-associated Listeria occurred during the first 3 days following infection, a relatively small (less than 2-fold) increase in number of Kupffer cell-associated Listeria was observed. The Listeria injected intravenously into immune animals, on the other hand, were eliminated rapidly from the hepatocyte as well as the Kupffer cell population. The latter findings suggest that uptake and elimination of pathogenic organisms by "nonprofessional phagocytes" in the liver (i.e., hepatocytes) may be an important effector mechanism in host defenses.