title: Particles from the Echinococcus granulosus laminated layer inhibit IL-4 and growth factor-driven Akt phosphorylation and proliferative responses in macrophages.
abstract: Proliferation of macrophages is a hallmark of inflammation in many type 2 settings including helminth infections. The cellular expansion is driven by the type 2 cytokine interleukin-4 (IL-4), as well as by M-CSF, which also controls homeostatic levels of tissue resident macrophages. Cystic echinococcosis, caused by the tissue-dwelling larval stage of the cestode Echinococcus granulosus, is characterised by normally subdued local inflammation. Infiltrating host cells make contact only with the acellular protective coat of the parasite, called laminated layer, particles of which can be ingested by phagocytic cells. Here we report that a particulate preparation from this layer (pLL) strongly inhibits the proliferation of macrophages in response to IL-4 or M-CSF. In addition, pLL also inhibits IL-4-driven up-regulation of Relm-α, without similarly affecting Chitinase-like 3 (Chil3/Ym1). IL-4-driven cell proliferation and up-regulation of Relm-α are both known to depend on the phosphatidylinositol (PI3K)/Akt pathway, which is dispensable for induction of Chil3/Ym1. Exposure to pLL in vitro inhibited Akt activation in response to proliferative stimuli, providing a potential mechanism for its activities. Our results suggest that the E. granulosus laminated layer exerts some of its anti-inflammatory properties through inhibition of PI3K/Akt activation and consequent limitation of macrophage proliferation.
authors.affiliation: Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) e Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay.
authors.forename: Paula I
authors.initials: PI
authors.lastname: Seoane
authors.affiliation: Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, UK.
authors.forename: Dominik
authors.initials: D
authors.lastname: Rückerl
authors.affiliation: Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) e Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Casaravilla
authors.affiliation: Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) e Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay.
authors.forename: Anabella A
authors.initials: AA
authors.lastname: Barrios
authors.affiliation: Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) e Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Pittini
authors.affiliation: Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester, UK.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: MacDonald
authors.affiliation: Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, UK.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Allen
authors.affiliation: Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) e Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Díaz
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation; D004443:Echinococcosis / Q000276:immunology*; D048209:Echinococcus granulosus / Q000378:metabolism*; D005260:Female; D015801:Helminth Proteins / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010587:Phagocytosis; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D015801:Helminth Proteins; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D051057:Proto-Oncogene Proteins c-akt