title: Dendritic-cell expression of Ship1 regulates Th2 immunity to helminth infection in mice.
abstract: In mouse models of infection with the gastrointestinal parasite Trichuris muris, appropriate dendritic-cell (DC) Ag sampling, migration, and presentation to T cells are necessary to mount a protective Th2-polarized adaptive immune response, which is needed to clear infection. SH2-containing inositol 5'-phosphatase 1 (SHIP-1) has been shown to be an important regulator of DC function in vitro through the negative regulation of the phosphoinositide 3-kinase (PI3K) pathway, but its role in vivo is relatively unexplored. In the current work, mice with a specific deletion of SHIP-1 in DCs (Ship1(ΔDC) ) were infected with the parasite T. muris. Ship1(ΔDC) mice were susceptible to infection due to ineffective priming of Th2-polarized responses. This is likely due to an increased production of interleukin (IL) 12p40 by SHIP-1-deficient DCs, as in vivo antibody blockade of IL-12p40 was able to facilitate the clearing of infection in Ship1(ΔDC) mice. Our results describe a critical role for SHIP-1 in regulating the ability of DCs to efficiently prime Th2-type responses.
authors.affiliation: Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gold
authors.affiliation: Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
authors.forename: Frann
authors.initials: F
authors.lastname: Antignano
authors.affiliation: Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hughes
authors.affiliation: Biomedical Research Centre, University of British Columbia, Vancouver, Canada.|Infection and Immunity Program, Monash Biomedicine Discovery Institute.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.
authors.forename: Colby
authors.initials: C
authors.lastname: Zaph
authors.affiliation: Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McNagny
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D000072181:Inositol Polyphosphate 5-Phosphatases; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology*; D014257:Trichuriasis / Q000276:immunology*; D014258:Trichuris / Q000276:immunology
chemical_list: D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
keywords: Dendritic cell ⋅ PI3K ⋅ SHIP-1 ⋅ Th2 ⋅ Trichuris muris