| Title: | Natural Killer T Cells Activated by a Lipopeptidophosphoglycan from Entamoeba histolytica Are Critically Important To Control Amebic Liver Abscess |
| Author: |
Lotter, Hannelore; González-Roldán, Nestor; Lindner, Buko; Isibasi, Armando; Moreno-Lafont, Martha; Ulmer, Artur J.; Holst, Otto; Tannich, Egbert; Jacobs, Thomas; Winau, Florian
Note: Order does not necessarily reflect citation order of authors. |
| 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. |
| Full Text & Related Files: |
2674934.pdf (658.6Kb; PDF)
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| 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. |
| Published Version: | doi:10.1371/journal.ppat.1000434 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674934/pdf/ |
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| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:4768785 |
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