Lipopolysaccharide Preconditioning Augments Phagocytosis of Malaria-Parasitized Red Blood Cells by Bone Marrow-Derived Macrophages in the Liver, Thereby Increasing the Murine Survival after Plasmodium yoelii Infection

Malaria remains a grave concern for humans, as effective medical countermeasures for infection have yet to be developed. Phagocytic clearance of parasitized red blood cells (pRBCs) by macrophages is an important front-line innate host defense against infection. We previously showed that repeated injections of low-dose lipopolysaccharide (LPS) prior to bacterial infection, called LPS preconditioning, strongly augmented phagocytic/bactericidal activity in murine macrophages. However, whether LPS preconditioning prevents murine infection is unclear. We investigated the protective effects of LPS preconditioning against lethal murine infection, focusing on CD11b F4/80 liver macrophages, which are increased by LPS preconditioning. Mice were subjected to LPS preconditioning by intraperitoneal injections of low-dose LPS for 3 consecutive days, and 24 h later, they were intravenously infected with pRBCs of Plasmodium yoelii 17XL. LPS preconditioning markedly increased the murine survival and reduced parasitemia, while it did not reduce tumor necrosis factor (TNF) secretions, only delaying the peak of plasma gamma interferon (IFN-γ) after infection in mice. An phagocytic clearance assay of pRBCs showed that the CD11b F4/80 liver macrophages, but not spleen macrophages, in the LPS-preconditioned mice had significantly augmented phagocytic activity against pRBCs. The adoptive transfer of CD11b F4/80 liver macrophages from LPS-preconditioned mice to control mice significantly improved survival after infection. We conclude that LPS preconditioning stimulated CD11b F4/80 liver macrophages to augment the phagocytic clearance of pRBCs, which may play a central role in resistance against infection.