Molecular structure of the “low molecular weight antigen” of Toxoplasma gondii: a glucose α1-4 N-acetylgalactosamine makes free glycosyl-phosphatidylinositols highly immunogenic

Striepen, Boris; Zinecker, Christina F.; Damm, Jan B. L.; Melgers, P A; Gerwig, Gerrit J.; Koolen, M. J. M.; Vliegenthart, Johannes F.G.; Dubremetz, Jean‐François; Schwarz, Ralph Τ.

doi:10.1006/jmbi.1996.0806

Cited by 98 publications

(84 citation statements)

References 53 publications

(43 reference statements)

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“…), which are common causes of disease in tropical areas. Our results confirm the findings of other researchers (26) and show no evidence of cross-reactivity.…”

Section: Vol 40 2002supporting

confidence: 93%

“…It has already been reported that the main targets for T. gondii-specific IgM in sera from patients with acute toxoplasmosis are carbohydrate branches (16) from GIPL present on the tachyzoite surface (9,26). Therefore, a practical and simple method was previously developed to enrich or purify these membrane compounds and test them as antigens in an indirect ELISA (9).…”

Section: Discussionmentioning

confidence: 99%

“…Different studies suggest that the main targets for T. gondii-specific IgM, present in sera from patients with acute toxoplasmosis, are carbohydrate branches from glycosylinositolphospholipids (GIPL) on the tachyzoite surface (9,26). An easy method of enriching or purifying the GIPLs derived from the tachyzoite stage of T. gondii was recently described (9).…”

mentioning

confidence: 99%

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Immunoglobulin M (IgM)-Glycoinositolphospholipid Enzyme-Linked Immunosorbent Assay: an Immunoenzymatic Assay for Discrimination between Patients with Acute Toxoplasmosis and Those with Persistent Parasite-Specific IgM Antibodies

et al. 2002

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In the present study we developed an enzyme-linked immunosorbent assay (ELISA) to measure immunoglobulin M (IgM) specific for glycoinositolphospholipids (GIPL) derived from tachyzoite membrane (IgM-GIPL ELISA). The sensitivity and specificity of the assay were compared with those of commercially available Toxoplasma-specific IgM serological tests, namely, immunofluorescence assay (IFA) with fixed tachyzoites and capture ELISA employing tachyzoite extracts. Our results show that all patients with acute toxoplasmosis, as determined by clinical data and conventional serological tests, were also positive by the IgM-GIPL ELISA. Interestingly, many patients that were classified as indeterminate, who had IgG with high avidity but positive results in the IgM-specific IFA and capture ELISA, were negative by the IgM-GIPL ELISA. Finally, we tested the sera from patients with rheumatoid arthritis and various parasitic infections and found no evidence of false positives in the IgM-GIPL ELISA.

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“…), which are common causes of disease in tropical areas. Our results confirm the findings of other researchers (26) and show no evidence of cross-reactivity.…”

Section: Vol 40 2002supporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Immunoglobulin M (IgM)-Glycoinositolphospholipid Enzyme-Linked Immunosorbent Assay: an Immunoenzymatic Assay for Discrimination between Patients with Acute Toxoplasmosis and Those with Persistent Parasite-Specific IgM Antibodies

et al. 2002

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“…A family of Parasite-specific glycosylphosphatidylinositols containing a novel glucosylated side chain has been shown to be highly immunogenic in humans (41). The following structures were identified: (ethanolamine-PO 4 )-Man␣1-2Man␣1-6(GalNAc␤1-4)Man␣1-4GlcN␣1-6-D-myo-inositol-PO 4 -lipid and (ethanolamine-PO 4 )-Man␣1-2Man␣1-6(Glc␣1-4GalNAc␤1-4)Man␣1-4GlcN␣1-6-D -myo-inositol-PO 4 -lipid both with and without terminal ethanolamine phosphate.…”

Section: Discussionmentioning

confidence: 99%

The Role of Inositol Acylation and Inositol Deacylation in the Toxoplasma gondii Glycosylphosphatidylinositol Biosynthetic Pathway

Smith

Kimmel

Azzouz

et al. 2007

Journal of Biological Chemistry

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Toxoplasma gondii is a ubiquitous parasitic protozoan that invades nucleated cells in a process thought to be in part due to several surface glycosylphosphatidylinositol (GPI)-anchored proteins, like the major surface antigen SAG1 (P30), which dominates the plasma membrane. The serine protease inhibitors phenylmethylsulfonyl fluoride and diisopropyl fluoride were found to have a profound effect on the T. gondii GPI biosynthetic pathway, leading to the observation and characterization of novel inositol-acylated mannosylated GPI intermediates. This inositol acylation is acyl-CoA-dependent and takes place before mannosylation, but uniquely for this class of inositol-acyltransferase, it is inhibited by phenylmethylsulfonyl fluoride. The subsequent inositol deacylation of fully mannosylated GPI intermediates is inhibited by both phenylmethylsulfonyl fluoride and diisopropyl fluoride. The use of these serine protease inhibitors allows observations as to the timing of inositol acylation and subsequent inositol deacylation of the GPI intermediates. Inositol acylation of the non-mannosylated GPI intermediate D-GlcN␣1-6-D-myo-inositol-1-HPO 4 -sn-lipid precedes mannosylation. Inositol deacylation of the fully mannosylated GPI intermediate allows further processing, i.e. addition of GalNAc side chain to the first mannose. Characterization of the phosphatidylinositol moieties present on both free GPIs and GPI-anchored proteins shows the presence of a diacylglycerol lipid, whose sn-2 position contains almost exclusively an C18:1 acyl chain. The data presented here identify key novel inositol-acylated mannosylated intermediates, allowing the formulation of an updated T. gondii GPI biosynthetic pathway along with identification of the putative genes involved.

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“…GPIs and non-GPI contaminants present in n-butyl alcohol were separated by precipitation of GPIs under a stream of nitrogen as described by Azzouz et al (2). The six different T. gondii GPIs (GPI I to GPI VI [39]) were then separated by TLC, with [ 3 H]glucosamine metabolically labeled T. gondii GPIs used as tracers. Chromatograms were scanned for radioactivity, and areas corresponding to individual T. gondii GPIs were scraped off, re-extracted with chloroform-methanol-water (10:10:3, by volume) by sonication (Branson 3200, 47 MHz; Branson Ultrasonics Corp., Danbury, CT), and recovered in the n-butyl alcohol phase after water-saturated n-butyl alcoholwater partition.…”

Section: Materials [mentioning

confidence: 99%

Fatty Acids Isolated from Toxoplasma gondii Reduce Glycosylphosphatidylinositol-Induced Tumor Necrosis Factor Alpha Production through Inhibition of the NF-κB Signaling Pathway

Debierre‐Grockiego¹,

Rabi²,

Schmidt³

et al. 2007

Infect Immun

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Glycosylphosphatidylinositols (GPIs) are involved in the pathogenicity of protozoan parasites and are known to induce inflammatory cytokines. However, we have previously shown that the family of six GPIs of Toxoplasma gondii extracted together from tachyzoites could not induce tumor necrosis factor alpha (TNF-␣) secretion by macrophages, whereas GPIs individually separated from this extract by thin-layer chromatography (TLC) were able to stimulate the cells. In the present study we show that the TLC step makes it possible to eliminate inhibitors extracted together with the T. gondii GPIs. Among the non-GPI molecules we have isolated fatty acids able to inhibit the secretion of TNF-␣ induced by the T. gondii GPIs. Myristic and palmitic acids reduce the production of TNF-␣ through the inhibition of tyrosine phosphorylation of cytoplasmic proteins and the inhibition of NF-B activation in a peroxisome proliferator-activated receptor-independent pathway and after a rapid entry into the cytoplasm of macrophages. GPIs are considered toxins inducing irreversible damage in the host, and fatty acids produced in parallel by the parasite could reduce the immune response, thus favoring the persistence of parasite infection.

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Molecular structure of the “low molecular weight antigen” of Toxoplasma gondii: a glucose α1-4 N-acetylgalactosamine makes free glycosyl-phosphatidylinositols highly immunogenic

Cited by 98 publications

References 53 publications

Immunoglobulin M (IgM)-Glycoinositolphospholipid Enzyme-Linked Immunosorbent Assay: an Immunoenzymatic Assay for Discrimination between Patients with Acute Toxoplasmosis and Those with Persistent Parasite-Specific IgM Antibodies

Immunoglobulin M (IgM)-Glycoinositolphospholipid Enzyme-Linked Immunosorbent Assay: an Immunoenzymatic Assay for Discrimination between Patients with Acute Toxoplasmosis and Those with Persistent Parasite-Specific IgM Antibodies

The Role of Inositol Acylation and Inositol Deacylation in the Toxoplasma gondii Glycosylphosphatidylinositol Biosynthetic Pathway

Fatty Acids Isolated from Toxoplasma gondii Reduce Glycosylphosphatidylinositol-Induced Tumor Necrosis Factor Alpha Production through Inhibition of the NF-κB Signaling Pathway

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