Loss of variable antigen during transformation of Trypanosoma brucei rhodesiense from bloodstream to procyclic forms in the tsetse fly

1988 ◽  
Vol 74 (6) ◽  
pp. 507-511 ◽  
Author(s):  
C. M. R. Turner ◽  
J. D. Barry ◽  
K. Vickerman
Keyword(s):  
Trypanosoma Brucei ◽  
Tsetse Fly ◽  
Trypanosoma Brucei Rhodesiense ◽  
Variable Antigen

Independent expression of the metacyclic and bloodstream variable antigen repertoires of Trypanosoma brucei rhodesiense

Parasitology ◽  
1986 ◽  
Vol 92 (1) ◽  
pp. 67-73 ◽  
Author(s):  
C. M. R. Turner ◽  
J. D. Barry ◽  
K. Vickerman
Keyword(s):  
Trypanosoma Brucei ◽  
Tsetse Fly ◽  
Trypanosoma Brucei Rhodesiense ◽  
Glossina Morsitans ◽  
Variable Antigen ◽  
Antigen Repertoire

SUMMARYThe variable antigen repertoire expressed by metacyclic Trypanosoma brucei rhodesiense is not influenced by the anamnestic expression whereby the variable antigen type (VAT) ingested by a tsetse fly is present at high levels in early bloodstream populations of fly-infected mice. This has been demonstrated by feeding to Glossina morsitans a trypanosome line expressing a VAT which is normally a component of the metacyclic repertoire. The VAT did not constitute a significantly increased proportion of the resultant metacyclic population which would have occurred had anamnestic expression and metacyclic expression been linked. Five other metacyclic VATs were also present at control levels. We conclude that the mechanisms of expression of VATs in the fly and in the mammal are independently controlled.

Trypanosome sociology and antigenic variation

Parasitology ◽  
1989 ◽  
Vol 99 (S1) ◽  
pp. S37-S47 ◽  
Author(s):  
K. Vickerman
Keyword(s):  
Trypanosoma Brucei ◽  
Antigenic Variation ◽  
Growth Characteristics ◽  
Tsetse Fly ◽  
Antigenic Specificity ◽  
Surface Coat ◽  
Humoral Immune ◽  
Variable Antigen ◽  
Minority Variants ◽  
Stimulation Of

SUMMARYSurvival of the trypanosome (Trypanosoma brucei) population in the mammalian body depends upon paced stimulation of the host's humoral immune response by different antigenic variants and serial sacrifice of the dominant variant (homotype) so that minority variants (heterotypes) can continue the infection and each become a homotype in its turn. New variants are generated by a spontaneous switch in gene expression so that the trypanosome puts on a surface coat of a glycoprotein differing in antigenic specificity from its predecessor. Homotypes appear in a characteristic order for a given trypanosome clone but what determines this order and the pacing of homotype generation so that the trypanosome does not quickly exhaust its repertoire of variable antigens, is not clear. The tendency of some genes to be expressed more frequently than others may reflect the location within the genome and mode of expression of the genes concerned and may influence homotype succession. Differences in the doubling time of different variants or in the rate at which trypanosomes belonging to a particular variant differentiate into non-dividing (vector infective) stumpy forms have also been invoked to explain how a heterotype's growth characteristics may determine when it becomes a homotype. Recent estimations of the frequency of variable antigen switching in trypanosome populations after transmission through the tsetse fly vector, however, suggest a much higher figure (0·97–2·2 × 10−3switches per cell per generation) than that obtained for syringe-passed infections (10−5–10−7switches per cell per generation) and it seems probable that most of the variable antigen genes are expressed as minority variable antigen types very early in the infection. Instability of expression is a feature of trypanosome clones derived from infective tsetse salivary gland (metacyclic) trypanosomes and it is suggested that high switching rates in tsetse-transmitted infections may delay the growth of certain variants to homotype status until later in the infection.

Onset of expression of the variant surface glycoproteins of Trypanosoma brucei in the tsetse fly studied using immunoelectron microscopy

1987 ◽  
Vol 87 (2) ◽  
pp. 363-372 ◽  
Author(s):  
L. Tetley ◽  
C.M. Turner ◽  
J.D. Barry ◽  
J.S. Crowe ◽  
K. Vickerman
Keyword(s):  
Trypanosoma Brucei ◽  
Tsetse Fly ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Fixed Sequence ◽  
Individual Variant ◽  
Variable Antigen ◽  
Variant Surface Glycoproteins ◽  
Scanning Electron

The acquisition of the variant surface glycoprotein (variable antigen) coat by metacyclic stage Trypanosoma brucei in the salivary glands of the tsetse fly, Glossina morsitans, has been studied in situ by transmission and scanning electron microscopy using monoclonal antibodies raised against metacyclic variable antigen types and complexed with horseradish peroxidase or colloidal gold. The coat is acquired after binary fission has ceased but while the parasite is still attached to the gland epithelium, i.e. before the mature metacyclic is released into the gland lumen. The variable antigen type heterogeneity previously observed in discharged mature metacyclics is here demonstrated in the nascent (attached) metacyclic population. The variant surface glycoprotein genes are thus not expressed in a fixed sequence since different metacyclic variable antigen types are present ab initio. The distribution of immunogold-marked nascent metacyclics of a particular variable antigen type, as shown by quadrat analysis of a scanning electron micrograph montage of the infected salivary gland epithelium, conforms to a Poisson series. This provides evidence that individual variant surface glycoprotein genes are stochastically activated and suggests that selective activation occurs after trypanosome division has ceased.

Antigenic variation in Trypanosoma brucei infections: an holistic view

1999 ◽  
Vol 112 (19) ◽  
pp. 3187-3192
Author(s):  
C.M. Turner
Keyword(s):  
Immune Responses ◽  
Trypanosoma Brucei ◽  
Antigenic Variation ◽  
Tsetse Fly ◽  
High Rate ◽  
T Helper 1 ◽  
Holistic View ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Variable Antigen

Trypanosoma brucei parasites undergo clonal phenotypic (antigenic) variation to promote their transmission between mammals and tsetse-fly vectors. This process is classically considered to be a mechanism for evading humoral immune responses, but such an explanation cannot account for the high rate of switching between variable antigens or for their hierarchical (i.e. non-random) expression. I suggest that these anomalies can be explained by a new model: that antigenic variation has evolved as a bifunctional, rather than as a unifunctional, strategy that not only evades humoral immune responses but also enables competition between parasite strains in concomitantly infected hosts. This competition causes a depression of cellular responses. My proposal gives rise to a number of testable predictions. First, low numbers of trypanosomes should express some variable antigen types (VATs) in infections several weeks before these VATs are detectable. Second, as an infection progresses, the number of VATs expressed simultaneously in the population should decrease. Third, immunisation to generate a T helper 1 response against those VATs that are expressed most frequently should lower parasitaemias and reduce virulence.

Differentiation in Trypanosoma brucei: host-parasite cell junctions and their persistence during acquisition of the variable antigen coat

1985 ◽  
Vol 74 (1) ◽  
pp. 1-19 ◽  
Author(s):  
L. Tetley ◽  
K. Vickerman
Keyword(s):  
Electron Microscopy ◽  
Trypanosoma Brucei ◽  
Morphological Changes ◽  
Freeze Fracture ◽  
Tsetse Fly ◽  
Cell Junctions ◽  
Surface Coat ◽  
Thin Sections ◽  
Variable Antigen ◽  
Host Parasite

Acquisition of the variable antigen-containing surface coat of Trypanosoma brucei occurs at the metacyclic stage in the salivary glands of the tsetse fly vector. The differentiation of the metacyclic trypanosome in the gland has been studied by scanning electron microscopy and by transmission electron microscopy of thin sections and freeze-fracture replicas. The uncoated epimastigote trypanosomes (with a prenuclear kinetoplast) divide while attached to the salivary gland epithelium brush border by elaborate branched flagellar outgrowths, which ramify between the host cell microvilli and form punctate hemidesmosome-like attachment plaques where they are indented by the microvilli. These outgrowths become reduced as the epimastigotes transform to uncoated trypomastigotes (with postnuclear kinetoplast), which remain attached and capable of binary fission. The flagellar outgrowths disappear but the attachment plaques persist as the uncoated trypomastigotes (premetacyclics) stop dividing and acquire the surface coat to become ‘nascent metacyclics’. Coat acquisition therefore occurs in the attached trypanosome and not, as previously believed, after detachment. Coating is accompanied by morphological changes in the glycosomes and mitochondrion of the parasite. Freeze-fracture replicas of the host-parasite junctional complexes show membrane particle aggregates on the host membrane but not on the parasite membrane. It is suggested that disruption of the complex occurs when maximum packing of the glycoprotein molecules has been achieved in the trypanosome surface coat, releasing the metacyclic trypanosome into the lumen of the gland.

scholarly journals Trypanosoma brucei rhodesiense Transmitted by a Single Tsetse Fly Bite in Vervet Monkeys as a Model of Human African Trypanosomiasis

2008 ◽  
Vol 2 (5) ◽  
pp. e238 ◽  
Author(s):  
John K. Thuita ◽  
John M. Kagira ◽  
David Mwangangi ◽  
Enock Matovu ◽  
C. M. R. Turner ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Human African Trypanosomiasis ◽  
Tsetse Fly ◽  
Vervet Monkeys ◽  
African Trypanosomiasis ◽  
Trypanosoma Brucei Rhodesiense

Neutralization of individual variable antigen types in metacyclic populations of Trypanosoma brucei does not prevent their subsequent expression in mice

Parasitology ◽  
1985 ◽  
Vol 90 (1) ◽  
pp. 79-88 ◽  
Author(s):  
J. D. Barry ◽  
J. S. Crowe ◽  
K. Vickerman
Keyword(s):  
Salivary Glands ◽  
Trypanosoma Brucei ◽  
Bloodstream Infections ◽  
Visual Observation ◽  
Tsetse Fly ◽  
Mammalian Host ◽  
Characteristic Set ◽  
Specific Antibodies ◽  
Antigenic Composition ◽  
Variable Antigen

The Trypanosoma brucei metacyclic population in the salivary glands of the tsetse fly displays a characteristic set of variable antigen types (VATs) which represents only a restricted part of the parasite's total VAT repertoire. After introduction into the mammalian host by fly bite, the metacyclics transform into bloodstream forms which retain expression of the metacyclic VATs. Specific antibodies, both polyvalent and monoclonal, have been used to neutralize separately 4 individual VATs from metacyclic populations. Control experiments and visual observation confirmed lysis of each VAT. On injection of the surviving trypanosomes, after washing, into mice each neutralized VAT was nevertheless expressed within a few days. Simultaneous neutralization of 2 metacyclic VATs which usually switch to one another in bloodstream infections did not prevent expression of either on subsequent injection into mice. Expression of neutralized VATs was not influenced by the antigenic composition of the population originally ingested by the tsetse fly. Metacyclic forms and their immediate successors thus appear to switch rapidly to expression of other metacyclic VATs in bloodstream populations.

Parasite development and host responses during the establishment of Trypanosoma brucei infection transmitted by tsetse fly

Parasitology ◽  
1984 ◽  
Vol 88 (1) ◽  
pp. 67-84 ◽  
Author(s):  
J. D. Barry ◽  
D. L. Emery
Keyword(s):  
Trypanosoma Brucei ◽  
Antigenic Variation ◽  
Tsetse Fly ◽  
Host Responses ◽  
Parasite Development ◽  
Large Mammals ◽  
Local Skin ◽  
Sequence Of Events ◽  
Draining Lymph Node ◽  
Variable Antigen

SUMMARYFollowing inoculation of Trypanosoma brucei into large mammals by the tsetse fly a local skin reaction, the ‘chancre’, develops due to trypanosome proliferation. We have cannulated the afferent and efferent lymphatics of the draining lymph node in goats and examined the onset of a cellular reaction, the emigration of the parasite from the chancre and the development of both antigenic variation and the specific immune response. The chancre first became detectable by day 3 post-infection, peaked by day 6 and then subsided. Lymphocyte output increased 6- to 8-fold by day 10 and the number of lymphoblasts increased 50-fold in this period. Both then declined. Trypanosomes were detected in lymph 1–2 days before the chancre, peaked by days 5–6, declined during development of the chancre and then peaked again. The bloodstream population appeared by days 4–5 and displayed different kinetics from that in lymph. Recirculation of parasites through the lymphatics ensued. Lymph-borne trypanosome populations were highly pleomorphic. Parasites in lymph expressed firstly a mixture of the Variable Antigen Types (VATs) which are found characteristically in the tsetse fly, this being followed by a mixture of other VATs. The two groups overlapped in appearance. In the bloodstream the same sequence of events occurred although 2 or 3 days later. The specific antibody response, as measured by radioimmunoassay and agglutination, arose within a few days of the first detection of each VAT. Activities appeared first in the lymph and then in plasma.

scholarly journals Characterization of the genes specifying two metacyclic variable antigen types in Trypanosoma brucei rhodesiense.

1984 ◽  
Vol 81 (21) ◽  
pp. 6642-6646 ◽  
Author(s):  
M. J. Lenardo ◽  
A. C. Rice-Ficht ◽  
G. Kelly ◽  
K. M. Esser ◽  
J. E. Donelson
Keyword(s):  
Trypanosoma Brucei ◽  
Trypanosoma Brucei Rhodesiense ◽  
Variable Antigen
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