Bacteria in the bloodstream are trapped in the liver and killed by immigrating neutrophils

Abstract

The critical role of the liver in the resolution of systemic bacterial infections is well documented. In the case of Listeria monocytogenes, approximately 60% of bacteria inoculated i.v. into mice are recovered in the liver at 10 min after infection. Here we report that the Listeria recovered at 10 min were distributed equally among the hepatocyte and nonparenchymal liver cell populations. The majority (>/= 75%) of these organisms were bound extracellularly as judged by their sensitivity to gentamicin. In contrast, >/= 93% of Listeria recovered in the liver at 6 h were located within hepatocytes. The listerial burden of the liver decreased 0.5 to 1.0 log, between 10 min and 6 h after infection. This decrease correlated with a sevenfold increase in the percentage of neutrophils that constituted the nonparenchymal cell population. Mice rendered neutrophil deficient by pretreatment with anti-granulocyte (RB6-8C5) mAb exhibited a significant increase (>300%) rather than a decrease in liver Listeria and a marked increase in hepatocyte damage. Similarly, neutrophil-deficient mice exhibited a reduced capacity to eliminate Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus that were cleared by the liver and bound extracellularly to hepatocytes and nonparenchymal cells. These findings document the crucial role of immigrating neutrophils in nonspecific host defenses to systemic bacterial infections expressed within the liver.