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

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

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dc.contributor.author Lotter, Hannelore
dc.contributor.author González-Roldán, Nestor
dc.contributor.author Lindner, Buko
dc.contributor.author Isibasi, Armando
dc.contributor.author Moreno-Lafont, Martha
dc.contributor.author Ulmer, Artur J.
dc.contributor.author Holst, Otto
dc.contributor.author Tannich, Egbert
dc.contributor.author Jacobs, Thomas
dc.contributor.author Winau, Florian
dc.date.accessioned 2011-03-23T00:38:05Z
dc.date.issued 2009
dc.identifier.citation Lotter, Hannelore, Nestor González-Roldán, Buko Lindner, Florian Winau, Armando Isibasi, Martha Moreno-Lafont, Artur J. Ulmer, Otto Holst, Egbert Tannich, and Thomas Jacobs. 2009. Natural killer T cells activated by a lipopeptidophosphoglycan from entamoeba histolytica are critically important to control amebic liver abscess. PLoS Pathogens 5(5): e1000434. en_US
dc.identifier.issn 1553-7366 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4768785
dc.description.abstract 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. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.ppat.1000434 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674934/pdf/ en_US
dash.license LAA
dc.subject biochemistry en_US
dc.subject macromolecular chemistry en_US
dc.subject immunology en_US
dc.subject innate immunity en_US
dc.subject leukocyte activation en_US
dc.subject infectious diseases en_US
dc.subject protozoal infections en_US
dc.subject tropical and travel-associated diseases en_US
dc.title Natural Killer T Cells Activated by a Lipopeptidophosphoglycan from Entamoeba histolytica Are Critically Important To Control Amebic Liver Abscess en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Pathogens en_US
dash.depositing.author Winau, Florian
dc.date.available 2011-03-23T00:38:05Z
dash.affiliation.other HMS^Pathology en_US

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