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Effector function of hepatocytes and Kupffer cells in the resolution of systemic bacterial infections
S H Gregory1, L K Barczynski, E J Wing
1Department of Medicine, University of Pittsburgh School of Medicine, Montefiore Hospital, PA 15213.
Abstract:
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 "non-professional phagocytes" in the liver (i.e., hepatocytes) may be an important effector mechanism in host defenses.
Insights
Listeria monocytogenes primarily replicates in liver hepatocytes, not Kupffer cells, in non-immune mice. Immune responses rapidly clear Listeria from both cell types, highlighting hepatocyte roles in host defense.
Area of Science:
- Immunology
- Hepatology
- Microbiology
Background:
- Mononuclear phagocytes, like Kupffer cells, are traditionally considered primary sites for intracellular pathogen replication.
- The specific role of liver cells in Listeria monocytogenes infection dynamics requires further elucidation.
Purpose of the Study:
- To investigate the proliferation sites of Listeria monocytogenes within the liver following intravenous injection.
- To determine the contribution of Kupffer cells versus hepatocytes to Listeria bacterial load.
Main Methods:
- Purification of hepatic cell populations (hepatocytes and Kupffer cells) from infected mice.
- Quantification of associated Listeria monocytogenes at various time points post-infection.
- Comparison of bacterial replication in non-immune and immune animal models.
Main Results:
- The majority of intravenously injected Listeria replicated within hepatocytes, showing a 200-fold increase in 3 days.
- Kupffer cells exhibited minimal Listeria proliferation (less than 2-fold increase).
- In immune mice, Listeria was rapidly eliminated from both hepatocytes and Kupffer cells.
Conclusions:
- Hepatocytes, considered non-professional phagocytes, are a major replication site for Listeria monocytogenes.
- Uptake and elimination by hepatocytes represent a significant host defense mechanism against this intracellular pathogen.
- Immune status dramatically influences the clearance of Listeria from liver cells.