Binding of Toxoplasma gondii Glycosylphosphatidylinositols to Galectin-3 Is Required for Their Recognition by Macrophages

Debierre‐Grockiego, Françoise; Niehus, Sebastian; Coddeville, Bernadette; Elass, Elisabeth; Poirier, Françoise; Weingart, Ralf; Schmidt, Richard R.; Mazurier, Joël; Guérardel, Yann; Schwarz, Ralph Τ.

doi:10.1074/jbc.m110.137588

Cited by 60 publications

(44 citation statements)

References 32 publications

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“…These findings are in line with several earlier studies that have shown that purified GPIs from protozoan parasites are able to activate immune cells of both myeloid and lymphoid origin [51]. In earlier work, we demonstrated that GPIs of RH and PTG strains bind with similar high affinities to human galectin-3 that is required to induce TNF-α secretion by macrophages in response to T. gondii GPIs [37]. Herein we showed that purified and individually tested GPIs from RH and PTG strains induce comparable secretion levels of TNF-α and IL-12 by macrophages, likely as a result of almost identical structures of GPI core glycans and lipid moieties.…”

Section: Discussionsupporting

confidence: 92%

Virulent and Avirulent Strains of Toxoplasma gondii Which Differ in Their Glycosylphosphatidylinositol Content Induce Similar Biological Functions in Macrophages

et al. 2014

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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.

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Section: Discussionsupporting

confidence: 92%

Virulent and Avirulent Strains of Toxoplasma gondii Which Differ in Their Glycosylphosphatidylinositol Content Induce Similar Biological Functions in Macrophages

et al. 2014

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“…The ligands expressed by T. gondii are recognized by tolllike receptors (TLR) [1][2][3] and stimulate IL-12 production via MyD88 signaling [4,5]. GPIanchored proteins of T. gondi is important for both adhesion to host and regulate host immune system via TLR2 and TLR4 on macrophage surface [2,3] aside profilin that secreted from T. gondii binds to TLR11 on dendritic cells [5].…”

Section: Molecular Basis Of Toxoplasmosismentioning

confidence: 99%

Toxoplasmosis and Public Health Genomics

Oymak¹,

Merve²,

Sevilay³

et al. 2017

Toxoplasmosis

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Toxoplasma gondii infection generally causes flu-like symptoms in healthy individuals; however, immunosuppression of the infected individual causes reactivation of the pathogen to its active form and relapse of the toxoplasmosis. Today it is known that toxoplasmosis triggers psychiatric disorders such as schizophrenia as well as behavioral changes such as suicide attempts. Although dermatological manifestations are very rare, the dermatological lesions are not unique. In addition, previous toxoplasma infection also causes congenital infections because of placental infection and causes birth defects and spontaneous abortion. T. gondii strains are mainly divided into three main clonal lineages, yet higher recombination rate causes unusual population structure and heterogeneous distribution of the pathogen. Both genetic variations, of the pathogen and the patients, are important for virulence property and success of the therapies. The scientist focuses on the genetic variations of the pathogens and individuals to achieve effective treatment and developed tailor-made medicines. Thus, understanding the molecular basis of the disease and the link of molecular mechanism with host immunity is important to fully know the disease and related disorders. In this chapter, we would like to evaluate the current knowledge on genetic, molecular characteristics of toxoplasmosis in view of public health genomics.

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“…However, Schwarz and colleagues have demonstrated that the glycophosphatidylinositol (GPIs) on the surface of Toxoplasma gondii can bind directly to galectin-3 on the surface of macrophages (45). The binding of these parasite GPIs to cell surface galectin-3, which associates with TLR2, is essential for TLR2-mediated production of tumor necrosis factor (TNF) α by the macrophages.…”

Section: Galectins Block Microbial Infectionmentioning

confidence: 99%

Microbeâ€“Host Interactions are Positively and Negatively Regulated by Galectinâ€“Glycan Interactions

et al. 2014

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Microbe–host interactions are complex processes that are directly and indirectly regulated by a variety of factors, including microbe presentation of specific molecular signatures on the microbial surface, as well as host cell presentation of receptors that recognize these pathogen signatures. Cell surface glycans are one important class of microbial signatures that are recognized by a variety of host cell lectins. Host cell lectins that recognize microbial glycans include members of the galectin family of lectins that recognize specific glycan ligands on viruses, bacteria, fungi, and parasites. In this review, we will discuss the ways that the interactions of microbial glycans with host cell galectins positively and negatively regulate pathogen attachment, invasion, and survival, as well as regulate host responses that mitigate microbial pathogenesis.

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Binding of Toxoplasma gondii Glycosylphosphatidylinositols to Galectin-3 Is Required for Their Recognition by Macrophages

Cited by 60 publications

References 32 publications

Virulent and Avirulent Strains of Toxoplasma gondii Which Differ in Their Glycosylphosphatidylinositol Content Induce Similar Biological Functions in Macrophages

Virulent and Avirulent Strains of Toxoplasma gondii Which Differ in Their Glycosylphosphatidylinositol Content Induce Similar Biological Functions in Macrophages

Toxoplasmosis and Public Health Genomics

Microbeâ€“Host Interactions are Positively and Negatively Regulated by Galectinâ€“Glycan Interactions

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