title: The Ly-6Chigh monocyte subpopulation transports Listeria monocytogenes into the brain during systemic infection of mice.
abstract: Mononuclear phagocytes can be used by intracellular pathogens to disseminate throughout the host. In the bloodstream these cells are generically referred to as monocytes. However, blood monocytes are a heterogeneous population, and the exact identity of the leukocyte(s) relevant for microbial spreading is not known. Experiments reported in this study used Listeria monocytogenes-infected mice to establish the phenotype of parasitized blood leukocytes and to test their role in systemic dissemination of intracellular bacteria. More than 90% of the blood leukocytes that were associated with bacteria were CD11b(+) mononuclear cells. Analysis of newly described monocyte subsets showed that most infected cells belonged to the Ly-6C(high) monocyte subset and that Ly-6C(high) and Ly-6C(neg-low) monocytes harbored similar numbers of bacteria per cell. Interestingly, systemic infection with wild-type or DeltaactA mutants of L. monocytogenes, both of which escape from phagosomes and replicate intracellularly, caused expansion of the Ly-6C(high) subset. In contrast, this was not evident after infection with Deltahly mutants, which neither escape phagosomes nor replicate intracellularly. Importantly, when CD11b(+) leukocytes were isolated from the brains of lethally infected mice, 88% of these cells were identified as Ly-6C(high) monocytes. Kinetic analysis showed a significant influx of Ly-6C(high) monocytes into the brain 2 days after systemic infection. This coincided with both bacterial invasion and up-regulation of brain macrophage chemoattractant protein-1 gene expression. These data indicate that the Ly-6C(high) monocyte subset transports L. monocytogenes into the brain and establish their role as Trojan horses in vivo.
authors.affiliation: Department of Medicine, Oklahoma University Health Sciences Center, and Veterans Affairs Medical Center, Oklahoma City, OK 73014, USA. douglas-drevets@ouhsc.edu
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Drevets
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Dillon
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Schawang
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Jan
authors.initials: J
authors.lastname: Ehrchen
authors.forename: Cord
authors.initials: C
authors.lastname: Sunderkötter
authors.forename: Pieter J M
authors.initials: PJ
authors.lastname: Leenen
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis*; D001692:Biological Transport / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D004660:Encephalitis / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D005260:Female; D016130:Immunophenotyping; D007424:Intracellular Fluid / Q000276:immunology / Q000382:microbiology; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000950:Antigens, Ly; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D011506:Proteins