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

View/ Open
Author
Lotter, Hannelore
González-Roldán, Nestor
Lindner, Buko
Isibasi, Armando
Moreno-Lafont, Martha
Ulmer, Artur J.
Holst, Otto
Tannich, Egbert
Jacobs, Thomas
Published Version
https://doi.org/10.1371/journal.ppat.1000434Metadata
Show full item recordCitation
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.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674934/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:4768785
Collections
- HMS Scholarly Articles [17875]
Contact administrator regarding this item (to report mistakes or request changes)