Both IgM and IgG anti-VSG antibodies initiate a cycle of aggregation–disaggregation of bloodstream forms of Trypanosoma brucei without damage to the parasite

O'Beirne, C; Lowry, Carolyn; Voorheis, H. Paul

doi:10.1016/s0166-6851(97)00191-6

Cited by 69 publications

(63 citation statements)

References 89 publications

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“…Endocytosis may be important for removing anti-VSG antibodies from the cell surface (Russo et al, 1993;O'Beirne et al, 1998); that is, up to a certain antibody level in the blood, the parasites may be able to evade Fc-receptor-mediated phagocytosis by macrophages. In fact, quantification in vitro of the rate of antibody endocytosis/degradation shows remarkably rapid kinetics of anti-VSG-IgG endocytosis (M.E., unpublished).…”

Section: Rates Of Vsg and Fluid-phase Endocytosismentioning

confidence: 99%

“…VSG is conveyed to endosomes by coated vesicles and indirect evidence suggests that it is efficiently recycled (Webster and Grab, 1988;Frevert and Reinwald, 1988;Seyfang et al, 1990;Grünfelder et al, 2003). Moreover, T. brucei clears anti-VSG antibodies from the cell surface (Russo et al, 1993;O'Beirne et al, 1998), and this process, in addition to the well-known antigenic variation, may contribute to parasite persistence in the immuno-competent host.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein inTrypanosoma brucei

Engstler

Thilo

Weise

et al. 2004

Journal of Cell Science

207

284

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Section: Rates Of Vsg and Fluid-phase Endocytosismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein inTrypanosoma brucei

Engstler

Thilo

Weise

et al. 2004

Journal of Cell Science

207

284

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“…It has been documented previously that IgG-VSG immune complexes are internalised by T. brucei and that, while the VSG is recycled to the surface, the IgG is degraded intracellularly (O'Beirne et al, 1998;Jeffries et al, 2001;Pal et al, 2003). Anti-VSG IgG has been located in RAB11-positive vesicles, but the peptidases involved in the degradation of IgG and their location within the cell have not been identified.…”

Section: Mca Null Mutants Are Viable In Vitro and In Vivomentioning

confidence: 99%

“…The surface VSG undergoes rapid internalisation and recycling (Seyfang et al, 1990) via the flagellar pocket, which is the only site of endocytosis and exocytosis for the parasite. This recycling may function as a secondary defence against immune challenge, aiding in the removal of host anti-VSG antibodies (O'Beirne et al, 1998). The antibodies are internalised, degraded and then secreted (Jeffries et al, 2001;Pal et al, 2003), although the enzymes responsible for degradation are yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Bloodstream formTrypanosoma bruceidepend upon multiple metacaspases associated with RAB11-positive endosomes

Helms

Ambit

Appleton

et al. 2006

Journal of Cell Science

101

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Trypanosoma brucei possesses five metacaspase genes. Of these, MCA2 and MCA3 are expressed only in the mammalian bloodstream form of the parasite, whereas MCA5 is expressed also in the insect procyclic form. Triple RNAi analysis showed MCA2, MCA3 and MCA5 to be essential in the bloodstream form, with parasites accumulating pre-cytokinesis. Nevertheless, triple null mutants (Δmca2/3Δmca5) could be isolated after sequential gene deletion. Thereafter, Δmca2/3Δmca5 mutants were found to grow well both in vitro in culture and in vivo in mice. We hypothesise that metacaspases are essential for bloodstream form parasites, but they have overlapping functions and their progressive loss can be compensated for by activation of alternative biochemical pathways. Analysis of Δmca2/3Δmca5 revealed no greater or lesser susceptibility to stresses reported to initiate programmed cell death, such as treatment with prostaglandin D2. The metacaspases were found to colocalise with RAB11, a marker for recycling endosomes. However, variant surface glycoprotein (VSG) recycling processes and the degradation of internalised anti-VSG antibody were found to occur similarly in wild type, Δmca2/3Δmca5 and triple RNAi induced parasites. Thus, the data provide no support for the direct involvement of T. brucei metacaspases in programmed cell death and suggest that the proteins have a function associated with RAB11 vesicles that is independent of known recycling processes of RAB11-positive endosomes.

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“…VSG is subsequently recycled back to the flagellar pocket in Rab11-positive endosomes (163). The internalization of VSG into late-endocytic compartments is likely to play a key role in preventing the accumulation of opsonic antibody on the surface coat of T. brucei BF (18,242,318,364) and may provide a rationale for why the rate of endocytosis in this developmental stage is massively up-regulated compared to that in other trypanosomatids.…”

Section: Intersection Of Secretory and Endocytic Pathwaysmentioning

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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Both IgM and IgG anti-VSG antibodies initiate a cycle of aggregation–disaggregation of bloodstream forms of Trypanosoma brucei without damage to the parasite

Cited by 69 publications

References 89 publications

Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein inTrypanosoma brucei

Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein inTrypanosoma brucei

Bloodstream formTrypanosoma bruceidepend upon multiple metacaspases associated with RAB11-positive endosomes

Secretory Pathway of Trypanosomatid Parasites

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