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Epithelial-Cell-Derived Phospholipase A2 Group 1B Is an Endogenous Anthelmintic.
Entwistle, Lewis J; Pelly, Victoria S; Coomes, Stephanie M; Kannan, Yashaswini; Perez-Lloret, Jimena; Czieso, Stephanie; Silva Dos Santos, Mariana; MacRae, James I; Collinson, Lucy; Sesay, Abdul; Nikolov, Nikolay; Metidji, Amina; Helmby, Helena; Hui, David Y; Wilson, Mark S.
Afiliação
  • Entwistle LJ; Allergy and Anti-helminth Immunity Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Pelly VS; Allergy and Anti-helminth Immunity Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Coomes SM; Allergy and Anti-helminth Immunity Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Kannan Y; Allergy and Anti-helminth Immunity Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Perez-Lloret J; Allergy and Anti-helminth Immunity Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Czieso S; Allergy and Anti-helminth Immunity Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Silva Dos Santos M; Metabolomics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • MacRae JI; Metabolomics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Collinson L; Electron Microscopy, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Sesay A; Advanced Sequencing Facility, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Nikolov N; Advanced Sequencing Facility, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Metidji A; AhR Immunity Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Helmby H; Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
  • Hui DY; Department of Pathology, Metabolic Disease Research Center, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
  • Wilson MS; Allergy and Anti-helminth Immunity Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Immunology Discovery, Genentech Inc., South San Francisco, CA 94080, USA. Electronic address: wilson.mark@gene.com.
Cell Host Microbe ; 22(4): 484-493.e5, 2017 Oct 11.
Article em En | MEDLINE | ID: mdl-29024642
ABSTRACT
Immunity to intestinal helminth infections has been well studied, but the mechanism of helminth killing prior to expulsion remains unclear. Here we identify epithelial-cell-derived phospholipase A2 group 1B (PLA2g1B) as a host-derived endogenous anthelmintic. PLA2g1B is elevated in resistant mice and is responsible for killing tissue-embedded larvae. Despite comparable activities of other essential type-2-dependent immune mechanisms, Pla2g1b-/- mice failed to expel the intestinal helminths Heligmosomoides polygyrus or Nippostrongylus brasiliensis. Expression of Pla2g1b by epithelial cells was dependent upon intestinal microbiota, adaptive immunity, and common-gamma chain-dependent signaling. Notably, Pla2g1b was downregulated in susceptible mice and inhibited by IL-4R-signaling in vitro, uncoupling parasite killing from expulsion mechanisms. Resistance was restored in Pla2g1b-/- mice by treating infective H. polygyrus L3 larvae with PLA2g1B, which reduced larval phospholipid abundance. These findings uncover epithelial-cell-derived Pla2g1b as an essential mediator of helminth killing, highlighting a previously overlooked mechanism of anti-helminth immunity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipídeos / Nematospiroides dubius / Infecções por Strongylida / Fosfolipases A2 do Grupo IB / Mucosa Intestinal / Nippostrongylus Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipídeos / Nematospiroides dubius / Infecções por Strongylida / Fosfolipases A2 do Grupo IB / Mucosa Intestinal / Nippostrongylus Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article