Virulent and avirulent strains of Toxoplasma gondii which differ in their glycosylphosphatidylinositol content induce similar biological functions in macrophages.
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 ∼ 34% of the protein-free GPIs as well as ∼ 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-α and IL-12p40, and initiated TLR4/MyD88-dependent NF-κBp65 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.
Institute for Virology, Laboratory of Parasitology, Philipps-University, Marburg, Germany ; UPR 9022 CNRS, Institute of Molecular and Cellular Biology, Strasbourg, France.
Sebastian
S
Niehus
Biomedical Sciences Research Complex, University of St Andrews, St Andrews, United Kingdom.
Terry K
TK
Smith
Institute for Virology, Laboratory of Parasitology, Philipps-University, Marburg, Germany.
Nahid
N
Azzouz
Research Center René Rachou, Oswaldo Cruz Foundation, Laboratory of Immunopathology, Belo Horizonte, Brazil.
Marco A
MA
Campos
UMR 5235 CNRS, University of Montpellier 2, Montpellier, France.
Jean-François
JF
Dubremetz
Research Center René Rachou, Oswaldo Cruz Foundation, Laboratory of Immunopathology, Belo Horizonte, Brazil ; Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil ; Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Ricardo T
RT
Gazzinelli
Institute for Virology, Laboratory of Parasitology, Philipps-University, Marburg, Germany ; UMR 8576 CNRS, Unit of Structural and Functional Glycobiology, University of, Lille, France.
Ralph T
RT
Schwarz
Institute for Virology, Laboratory of Parasitology, Philipps-University, Marburg, Germany ; UMR 1282 Infectiology and Public Health, University of Tours, Tours, France and INRA, Nouzilly, France.
Françoise
F
Debierre-Grockiego
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D008264:Macrophages / Q000469:parasitology*; D051379:Mice; D014122:Toxoplasma / Q000378:metabolism* / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014709:Vero Cells
D017261:Glycosylphosphatidylinositols; D053762:Interleukin-12 Subunit p40; D014409:Tumor Necrosis Factor-alpha