Glycosyl-phosphatidylinositols of : Two Common Precursors but a New Protein-anchor

Gerold, Peter; Striepen, Boris; Reitter, Barbara E.; Geyer, Hildegard; Geyer, Rudolf; Reinwald, E.; Risse, H. J.; Schwarz, Ralph Τ.

doi:10.1006/jmbi.1996.0451

Cited by 30 publications

(20 citation statements)

References 26 publications

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“…Anti-VSG antibodies induce T. congolense to shed VSG [51]. This process might expose invariant surface epitopes, such as the conserved VSG carbohydrates [52,53]. The glycan of the GPI anchor of the VSG contains three mannose molecules [52].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

CR3 (CD11b/CD18) is the major macrophage receptor for IgM antibody-mediated phagocytosis of African trypanosomes: Diverse effect on subsequent synthesis of tumor necrosis factor α and nitric oxide

Pan

Ogunremi

Wei

et al. 2006

Microbes and Infection

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Section: Discussionmentioning

confidence: 99%

“…This process might expose invariant surface epitopes, such as the conserved VSG carbohydrates [52,53]. The glycan of the GPI anchor of the VSG contains three mannose molecules [52]. Mannose receptor of macrophages might recognize these carbohydrate epitopes and further mediate phagocytosis.…”

Section: Discussionmentioning

confidence: 99%

CR3 (CD11b/CD18) is the major macrophage receptor for IgM antibody-mediated phagocytosis of African trypanosomes: Diverse effect on subsequent synthesis of tumor necrosis factor α and nitric oxide

Pan

Ogunremi

Wei

et al. 2006

Microbes and Infection

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“…African trypanosomes cause persistent infections of the blood. They survive in the blood stream of humans and animals by complex evasion mechanisms (2), including antigenic variation (3)(4)(5) and immunosuppression (6 -10). In the mammalian host, the whole parasite is coated with a glycoprotein coat of a single molecular species, called the variant surface glycoprotein (VSG), 3 which is anchored into the membrane via a glycolipid, GPI (4,5).…”

Section: Trypanosoma Brucei Gambiense and Trypanosoma Brucei Rhodesiementioning

confidence: 99%

Regulatory T Cells Prevent Control of Experimental African Trypanosomiasis

Wei

Tabel

2008

The Journal of Immunology

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African trypanosomes are single-cell, extra-cellular blood parasites causing profound immunosuppression. Susceptible BALB/c mice infected s.c. into a footpad with 104 Trypanosoma congolense die with fulminating parasitemia within 10 days. We injected BALB/c mice 2 days before such an infection with different doses of a depleting mAb specific for CD25, a surface marker of regulatory T cells (Tregs). Pretreatment with a low, optimal dose of anti-CD25 resulted in a dramatic effect, in that the infected mice did not develop parasitemia, as well as eliminated all parasites and showed no signs of disease. Their spleens showed a 100% reduction of CD4+CD25high T cells and overall a 70% reduction of CD4+CD25+Foxp3+ T cells 7 days postinfection. The protective effect of treatment with an optimal dose of anti-CD25 could be reversed by administration of l-N6-(1-imminoethyl) lysine, a specific inhibitor of inducible NO synthase or administration of anti-CD8 Ab. Analysis of the cytokine patterns and cell surface marker in infected mice pretreated with anti-CD25 Abs pointed to a potential NKT cell response. We then conducted infections in CD1d−/− mice. From our observations, we conclude that CD4+CD25highFoxp3+ Tregs prevent, in normal infected susceptible mice, an early protective response mediated by CD8+ NKT cell-dependent activation of macrophages to kill parasites by production of NO. Our results also indicate that different populations of NKT cells have protective or suppressive effects. Our observations lead us to propose a hypothesis of cross-regulation of NKT cells and Tregs in trypanosome infections.

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“…In support of this notion, a small proportion of the free GPIs in T. brucei BF are modified with galactose residues to the same extent, regardless of VSG subtype (196). In T. congolense BF, the VSG anchor is modified with a novel Gal␤1-6GlcNAc side chain that is added to the first core mannose residue (118). In addition, the lipid moieties of the VSG anchors can undergo further rounds of fatty acid remodeling in the Golgi or post-Golgi compartment, in which preexisting myristic acid is replaced with another myristic acid (54).…”

Section: Biosynthesis Of Gpi Protein Anchorsmentioning

confidence: 99%

Secretory Pathway of Trypanosomatid Parasites

McConville

Mullin

Ilgoutz

et al. 2002

Microbiol Mol Biol Rev

222

191

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The Trypanosomatidae comprise a large group of parasitic protozoa, some of which cause important diseases in humans. These include Trypanosoma brucei (the causative agent of African sleeping sickness and nagana in cattle), Trypanosoma cruzi (the causative agent of Chagas' disease in Central and South America), and Leishmania spp. (the causative agent of visceral and [muco]cutaneous leishmaniasis throughout the tropics and subtropics). The cell surfaces of these parasites are covered in complex protein- or carbohydrate-rich coats that are required for parasite survival and infectivity in their respective insect vectors and mammalian hosts. These molecules are assembled in the secretory pathway. Recent advances in the genetic manipulation of these parasites as well as progress with the parasite genome projects has greatly advanced our understanding of processes that underlie secretory transport in trypanosomatids. This article provides an overview of the organization of the trypanosomatid secretory pathway and connections that exist with endocytic organelles and multiple lytic and storage vacuoles. A number of the molecular components that are required for vesicular transport have been identified, as have some of the sorting signals that direct proteins to the cell surface or organelles in the endosome-vacuole system. Finally, the subcellular organization of the major glycosylation pathways in these parasites is reviewed. Studies on these highly divergent eukaryotes provide important insights into the molecular processes underlying secretory transport that arose very early in eukaryotic evolution. They also reveal unusual or novel aspects of secretory transport and protein glycosylation that may be exploited in developing new antiparasite drugs

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Glycosyl-phosphatidylinositols of : Two Common Precursors but a New Protein-anchor

Cited by 30 publications

References 26 publications

CR3 (CD11b/CD18) is the major macrophage receptor for IgM antibody-mediated phagocytosis of African trypanosomes: Diverse effect on subsequent synthesis of tumor necrosis factor α and nitric oxide

CR3 (CD11b/CD18) is the major macrophage receptor for IgM antibody-mediated phagocytosis of African trypanosomes: Diverse effect on subsequent synthesis of tumor necrosis factor α and nitric oxide

Regulatory T Cells Prevent Control of Experimental African Trypanosomiasis

Secretory Pathway of Trypanosomatid Parasites

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