Department of Medicine, Division of Infectious Diseases and Immunology
Immunity | Parasitic Diseases | Parasitology
Glycosylphosphatidylinositols (GPIs) from several protozoan parasites are thought to elicit a detrimental stimulation of the host innate immune system aside their main function to anchor surface proteins. Here we analyzed the GPI biosynthesis of an avirulent Toxoplasma gondii type 2 strain (PTG) by metabolic radioactive labeling. We determined the biological function of individual GPI species in the PTG strain in comparison with previously characterized GPI-anchors of a virulent strain (RH). The GPI intermediates of both strains were structurally similar, however the abundance of two of six GPI intermediates was significantly reduced in the PTG strain. The side-by-side comparison of GPI-anchor content revealed that the PTG strain had only approximately 34% of the protein-free GPIs as well as approximately 70% of the GPI-anchored proteins with significantly lower rates of protein N-glycosylation compared to the RH strain. All mature GPIs from both strains induced comparable secretion levels of TNF-alpha and IL-12p40, and initiated TLR4/MyD88-dependent NF-kappaBp65 activation in macrophages. Taken together, these results demonstrate that PTG and RH strains differ in their GPI biosynthesis and possess significantly different GPI-anchor content, while individual GPI species of both strains induce similar biological functions in macrophages.
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© 2014 Niehus et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS One. 2014 Jan 28;9(1):e85386. doi: 10.1371/journal.pone.0085386. eCollection 2014.Link to article on publisher's site
Niehus, Sebastian; Smith, Terry K.; Azzouz, Nahid; Campos, Marco A.; Dubremetz, Jean-Francois; Gazzinelli, Ricardo T.; Schwarz, Ralph T.; and -Grockiego, Francoise Debierre, "Virulent and avirulent strains of Toxoplasma gondii which differ in their glycosylphosphatidylinositol content induce similar biological functions in macrophages" (2014). University of Massachusetts Medical School Faculty Publications. 438.
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