title: Myeloid cell-specific expression of Ship1 regulates IL-12 production and immunity to helminth infection.
abstract: Helminth infection leads to the local proliferation and accumulation of macrophages in tissues. However, the function of macrophages during helminth infection remains unclear. SH2-containing inositol 5'-phosphatase 1 (Ship1, Inpp5d) is a lipid phosphatase that has been shown to play a critical role in macrophage function. Here, we identify a critical role for Ship1 in the negative regulation of interleukin (IL)-12/23p40 production by macrophages during infection with the intestinal helminth parasite Trichuris muris. Mice with myeloid cell-specific deletion of Ship1 (Ship1(ΔLysM) mice) develop a non-protective T-helper type 1 cell response and fail to expel parasites. Ship1-deficient macrophages produce heightened levels of IL-12/23p40 in vitro and in vivo and antibody blockade of IL-12/23p40 renders Ship1(ΔLysM) mice resistant to Trichuris infection. Our results identify a critical role for the negative regulation of IL-12/23p40 production by macrophages in the development of a protective T(H)2 cell response.
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Hadidi
authors.forename: F
authors.initials: F
authors.lastname: Antignano
authors.forename: M R
authors.initials: MR
authors.lastname: Hughes
authors.forename: S K H
authors.initials: SK
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Snyder
authors.forename: G M
authors.initials: GM
authors.lastname: Sammis
authors.forename: W G
authors.initials: WG
authors.lastname: Kerr
authors.forename: K M
authors.initials: KM
authors.lastname: McNagny
authors.forename: C
authors.initials: C
authors.lastname: Zaph
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000235:genetics; D007109:Immunity; D000072181:Inositol Polyphosphate 5-Phosphatases; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D007411:Intestinal Diseases, Parasitic / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D022423:Myeloid Cells / Q000378:metabolism; D009928:Organ Specificity; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014257:Trichuriasis / Q000276:immunology*; D014258:Trichuris / Q000276:immunology*
chemical_list: D018664:Interleukin-12; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases