Dissemination of Listeria monocytogenes by infected phagocytes

In vitro data suggest that blood-borne Listeria monocytogenes organisms enter the central nervous system (CNS) by direct invasion of endothelial cells or by cell-to-cell spread from infected phagocytes to endothelial cells. However, a role for infected phagocytes in neuroinvasion and dissemination of L. monocytogenes in vivo has not been confirmed experimentally. Experiments described here tested whether L. monocytogenes-infected peripheral blood leukocytes (PBL) circulated in bacteremic mice and could establish organ infection in vivo. A mean of 30.5% of bacteria cultured from whole blood were PBL associated, and microscopy showed that 22.2% of monocytes and 1.6% of neutrophils were infected. PBL-associated bacteria spread to endothelial cells in vitro, indicating their potential for virulence in vivo. To test this possibility, mice were injected intravenously with infected PBL and CFU of bacteria in liver, spleen, and brain were quantified and compared with values for mice injected with broth-grown bacteria and in vitro-infected macrophage cell lines. An inoculum of infected macrophage cell lines led to greater numbers of bacteria in the liver than the numbers produced by a similar inoculum of broth-grown bacteria. In contrast, brain infection was best established by infected PBL. Results of intraperitoneal injection of infected peritoneal cells compared with results of injection with infected J774A.1 cells suggested that unrestricted intracellular bacterial replication within J774A.1 cells contributed to excessive liver infection in those mice. These data show dissemination of intracellular L. monocytogenes and indicate that phagocyte-facilitated invasion has a role in CNS infection in vivo. Heterogeneity with regard to bactericidal activity as well as to other phagocyte characteristics is a critical feature of this mechanism.