title: Liver dendritic cells present bacterial antigens and produce cytokines upon Salmonella encounter.
abstract: The capacity of murine liver dendritic cells (DC) to present bacterial Ags and produce cytokines after encounter with Salmonella was studied. Freshly isolated, nonparenchymal liver CD11c(+) cells had heterogeneous expression of MHC class II and CD11b and a low level of CD40 and CD86 expression. Characterization of liver DC subsets revealed that CD8alpha(-)CD4(-) double negative cells constituted the majority of liver CD11c(+) ( approximately 85%) with few cells expressing CD8alpha or CD4. Flow cytometry analysis of freshly isolated CD11c(+) cells enriched from the liver and cocultured with Salmonella expressing green fluorescent protein (GFP) showed that CD11c(+) MHC class II(high) cells had a greater capacity to internalize Salmonella relative to CD11c(+) MHC class II(low) cells. Moreover, both CD8alpha(-) and CD8alpha(+) liver DC internalized bacteria with similar efficiency after both in vitro and in vivo infection. CD11c(+) cells enriched from the liver could also process Salmonella for peptide presentation on MHC class I and class II to primary, Ag-specific T cells after internalization requiring actin cytoskeletal rearrangements. Flow cytometry analysis of liver CD11c(+) cells infected with Salmonella expressing GFP showed that both CD8alpha(-) and CD8alpha(+) DC produced IL-12p40 and TNF-alpha. The majority of cytokine-positive cells did not contain bacteria (GFP(-)) whereas only a minor fraction of cytokine-positive cells were GFP(+). Furthermore, only approximately 30-50% of liver DC containing bacteria (GFP(+)) produced cytokines. Thus, liver DC can internalize and process Salmonella for peptide presentation to CD4(+) and CD8(+) T cells and elicit proinflammatory cytokine production upon Salmonella encounter, suggesting that DC in the liver may contribute to immunity against hepatotropic bacteria.
authors.affiliation: Department of Cell and Molecular Biology, Section for Immunology, Lund University, Lund, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Johansson
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Wick
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D016827:CD8 Antigens / Q000096:biosynthesis; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D008024:Ligands; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D008565:Membrane Proteins / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010587:Phagocytosis / Q000276:immunology; D012486:Salmonella typhimurium / Q000254:growth & development / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D016827:CD8 Antigens; C431698:CD8alpha antigen; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D008565:Membrane Proteins; C084881:flt3 ligand protein