In vivo Lipopolysaccharide Tolerance Recruits CD11b+ Macrophages to the Liver with Enhanced Bactericidal Activity and Low Tumor Necrosis Factor-Releasing Capability, Resulting in Drastic Resistance to Lethal Septicemia

Objectives: In vivo lipopolysaccharide (LPS) tolerance on bacterial infection was investigated, focusing on liver macrophages. Methods: LPS tolerance was induced by intraperitoneal injections with 5 mu g/kg of LPS for 3 consecutive days, and then mice were intravenously infected with Escherichia coli. Results: All LPS-primed mice survived lethal bacterial infection. Drastic enhancement of bactericidal activity of liver macrophages strongly contributed to bacterial clearance. Although LPS-primed mice produced substantial amounts of tumor necrosis factor (TNF) inside the liver, TNF efflux into the systemic circulation was markedly suppressed. These mice showed a dramatic increase in CD11b(+) monocytederived macrophages in the liver. The CD11b(+) macrophages that increased in LPS-primed mice were those with strong phagocytic/bactericidal activity and an upregulated expression of Fc. receptor I, but the subfraction with a potent TNFproducing capacity and poor phagocytic activity diminished. The adoptive transfer of CD11b(+) macrophages from LPS-primed mice to control mice increased survival after bacterial infection and reduced the elevation of plasma TNF. LPS priming did not affect the CD68(+) resident Kupffer cells, and CD68(+) Kupffer cell-depleted mice still exhibited LPS tolerance with strong resistance to bacteremia. Conclusions: LPS tolerance recruits CD11b(+) macrophages to the liver with enhanced bactericidal activity, which plays a central role in resistance to lethal bacteremia. (C) 2017 S. Karger AG, Basel