Natural Killer T Cells Activated by a Lipopeptidophosphoglycan from Entamoeba histolytica Are Critically Important To Control Amebic Liver Abscess

PLoS Pathogens

Hannelore Lotter¹  Nestor González-Roldán¹  Egbert Tannich²  Armando Isibasi²  Martha Moreno-Lafont³  Thomas Jacobs⁴  Buko Lindner⁵  Artur J. Ulmer⁶  Florian Winau⁷  Otto Holst⁷ 

[1] Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany;Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico;Division of Immunochemistry, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany;Division of Immunology and Cell Biology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany;Division of Structural Biochemistry, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany;Immune Disease Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts, United States of America;Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI del Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico

关键词: Antigen-presenting cells;    Entamoeba histolytica;    Mouse models;    Abscesses;    Trophozoites;    Lymphocytes;    Cell activation;    Glycolipids;   

DOI  :  10.1371/journal.ppat.1000434

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The innate immune response is supposed to play an essential role in the control of amebic liver abscess (ALA), a severe form of invasive amoebiasis due to infection with the protozoan parasite Entamoeba histolytica. In a mouse model for the disease, we previously demonstrated that Jα18-/- mice, lacking invariant natural killer T (iNKT) cells, suffer from more severe abscess development. Here we show that the specific activation of iNKT cells using α-galactosylceramide (α-GalCer) induces a significant reduction in the sizes of ALA lesions, whereas CD1d−/− mice develop more severe abscesses. We identified a lipopeptidophosphoglycan from E. histolytica membranes (EhLPPG) as a possible natural NKT cell ligand and show that the purified phosphoinositol (PI) moiety of this molecule induces protective IFN-γ but not IL-4 production in NKT cells. The main component of EhLPPG responsible for NKT cell activation is a diacylated PI, (1-O-[(28∶0)-lyso-glycero-3-phosphatidyl-]2-O-(C16:0)-Ins). IFN-γ production by NKT cells requires the presence of CD1d and simultaneously TLR receptor signalling through MyD88 and secretion of IL-12. Similar to α-GalCer application, EhLPPG treatment significantly reduces the severity of ALA in ameba-infected mice. Our results suggest that EhLPPG is an amebic molecule that is important for the limitation of ALA development and may explain why the majority of E. histolytica-infected individuals do not develop amebic liver abscess.

【 授权许可】

CC BY