title: T-zone localized monocyte-derived dendritic cells promote Th1 priming to Salmonella.
abstract: Control of intracellular Salmonella infection requires Th1 priming and IFN-γ production. Here, we show that efficient Th1 priming after Salmonella infection requires CD11c(+) CD11b(hi) F4/80(+) monocyte-derived dendritic cells (moDCs). In non-infected spleens, moDCs are absent from T-cell zones (T zones) of secondary lymphoid tissues, but by 24 h post-infection moDCs are readily discernible in these sites. The accumulation of moDCs is more dependent upon bacterial viability than bacterial virulence. Kinetic studies showed that moDCs were necessary to prime but not sustain Th1 responses, while ex vivo studies showed that antigen-experienced moDCs were sufficient to induce T-cell proliferation and IFN-γ production via a TNF-α-dependent mechanism. Importantly, moDCs and cDCs when co-cultured induced superior Th1 differentiation than either subset alone, and this activity was independent of TNF-α. Thus, optimal Th1 development to Salmonella requires the rapid accumulation of moDCs within T zones and their collaboration with cDCs.
authors.affiliation: Medical Research Council Centre for Immune Regulation, School of Immunity and Infection, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
authors.forename: Adriana
authors.initials: A
authors.lastname: Flores-Langarica
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Marshall
authors.forename: Saeeda
authors.initials: S
authors.lastname: Bobat
authors.forename: Elodie
authors.initials: E
authors.lastname: Mohr
authors.forename: Jessica
authors.initials: J
authors.lastname: Hitchcock
authors.forename: Ewan A
authors.initials: EA
authors.lastname: Ross
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Coughlan
authors.forename: Mahmood
authors.initials: M
authors.lastname: Khan
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Ian R
authors.initials: IR
authors.lastname: Henderson
authors.forename: Ian C M
authors.initials: IC
authors.lastname: Maclennan
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000943:Antigens, Differentiation / Q000096:biosynthesis; D039481:CD11b Antigen / Q000096:biosynthesis; D039521:CD11c Antigen / Q000096:biosynthesis; D002450:Cell Communication; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000473:pathology; D012475:Salmonella / Q000276:immunology* / Q000472:pathogenicity; D012480:Salmonella Infections / Q000276:immunology*; D013154:Spleen / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D039481:CD11b Antigen; D039521:CD11c Antigen; D014409:Tumor Necrosis Factor-alpha; C036763:monocyte-macrophage differentiation antigen; D007371:Interferon-gamma