title: A central role for hepatic conventional dendritic cells in supporting Th2 responses during helminth infection.
abstract: Dendritic cells (DCs) are the key initiators of T-helper (Th) 2 immune responses against the parasitic helminth Schistosoma mansoni. Although the liver is one of the main sites of antigen deposition during infection with this parasite, it is not yet clear how distinct DC subtypes in this tissue respond to S. mansoni antigens in vivo, or how the liver microenvironment might influence DC function during establishment of the Th2 response. In this study, we show that hepatic DC subsets undergo distinct activation processes in vivo following murine infection with S. mansoni. Conventional DCs (cDCs) from schistosome-infected mice upregulated expression of the costimulatory molecule CD40 and were capable of priming naive CD4(+) T cells, whereas plasmacytoid DCs (pDCs) upregulated expression of MHC class II, CD86 and CD40 but were unable to support the expansion of either naive or effector/memory CD4(+) T cells. Importantly, in vivo depletion of pDCs revealed that this subset was dispensable for either maintenance or regulation of the hepatic Th2 effector response during acute S. mansoni infection. Our data provides strong evidence that S. mansoni infection favors the establishment of an immunogenic, rather than tolerogenic, liver microenvironment that conditions cDCs to initiate and maintain Th2 immunity in the context of ongoing antigen exposure.
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UK.|Centre for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Lundie
authors.affiliation: Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, UK.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Webb
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UK.
authors.forename: Angela K
authors.initials: AK
authors.lastname: Marley
authors.affiliation: Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, UK.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Phythian-Adams
authors.affiliation: Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, UK.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Cook
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UK.
authors.forename: Lucy H
authors.initials: LH
authors.lastname: Jackson-Jones
authors.affiliation: Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, UK.
authors.forename: Sheila
authors.initials: S
authors.lastname: Brown
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UK.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Maizels
authors.affiliation: EPIRUS Biopharmaceuticals, Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia.
authors.forename: Meredith
authors.initials: M
authors.lastname: O'Keeffe
authors.affiliation: Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, UK.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: MacDonald
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology; D008099:Liver / Q000276:immunology* / Q000469:parasitology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000947:Antigens, Helminth