1. 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.
- Author
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Kinoshita M, Miyazaki H, Nakashima H, Nakashima M, Nishikawa M, Ishikiriyama T, Kato S, Iwaya K, Hiroi S, Shinomiya N, and Seki S
- Subjects
- Animals, Bacteriolysis, CD11b Antigen metabolism, Cell Movement, Cells, Cultured, Immune Tolerance, Immunity, Injections, Intraperitoneal, Male, Mice, Mice, Inbred C57BL, Phagocytosis, Receptors, IgG metabolism, Tumor Necrosis Factor-alpha metabolism, Escherichia coli immunology, Escherichia coli Infections immunology, Lipopolysaccharides immunology, Liver pathology, Macrophages immunology, Sepsis immunology
- Abstract
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 μg/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+ monocyte- derived 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 Fcγ receptor I, but the subfraction with a potent TNF-producing 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., (© 2017 S. Karger AG, Basel.)
- Published
- 2017
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