Clearance of trypanosomes from the blood of infected Cape buffalo was associated with the development of two responses: (i) complement-dependent and clone-specific lytic activity and (ii) complement-independent trypanocidal activity that was not restricted by trypanosome clone or species. This latter activity was mediated by H2O2 and required the presence of xanthine oxidase in serum but not the addition of purine substrates. Expression of the xanthine oxidase-dependent trypanocidal activity in Cape buffalo serum was coincident with, and required, a decline in its H2O2 catabolic activity. The H2O2 catabolic activity of Cape buffalo serum was due solely to catalase and declined by eightfold around the time that trypanosomes were cleared from the blood, accompanied by a fivefold drop in erythrocyte-associated catalase activity. The Cape buffalo did not develop subsequent parasitemic waves. Clearance of parasitemia in similarly infected cattle was also associated with development of trypanosome clone-specific lytic activity, but not with the acquisition of H2O2-dependent trypanocidal activity in serum, and the cattle supported recurring parasitemia. The lack of trypanocidal activity in pre- and postinfection cattle sera was due to their low content of xanthine oxidase and sustained catalase activity. These data strongly suggest that an infection-induced serum oxidative response, the efficacy of which is amplified by a decline in blood catalase, contributes to suppression of recurring parasitemia in Cape buffalo. (+info)
Minisatellite marker analysis of Trypanosoma brucei: reconciliation of clonal, panmictic, and epidemic population genetic structures.
(2/68)
The African trypanosome, Trypanosoma brucei, has been shown to undergo genetic exchange in the laboratory, but controversy exists as to the role of genetic exchange in natural populations. Much of the analysis to date has been derived from isoenzyme or randomly amplified polymorphic DNA data with parasite material from a range of hosts and geographical locations. These markers fail to distinguish between the human infective (T. b. rhodesiense) and nonhuman infective (T. b. brucei) "subspecies" so that parasites derived from hosts other than humans potentially contain both subspecies. To overcome some of the inherent problems with the use of such markers and diverse populations, we have analyzed a well-defined population from a discrete geographical location (Busoga, Uganda) using three recently described minisatellite markers. The parasites were primarily isolated from humans and cattle with the latter isolates further characterized by their ability to resist lysis by human serum (equivalent to human infectivity). The minisatellite markers show high levels of polymorphism, and from the data obtained we conclude that T. b. rhodesiense is genetically isolated from T. b. brucei and can be unambiguously identified by its multilocus genotype. Analysis of the genotype frequencies in the separated T. b. brucei and T. b. rhodesiense populations shows the former has an epidemic population structure whereas the latter is clonal. This finding suggests that the strong linkage disequilibrium observed in previous analyses, where human and nonhuman infective trypanosomes were not distinguished, results from the treatment of two genetically isolated populations as a single population. (+info)
Bovine leukosis. IV. Trypanosomiasis, lymphocytosis and DNA synthesis.
(3/68)
The possible influence of natural trypanosome infection on lymphocytosis and DNA synthesizing lymphocyte counts in peripheral blood was determined on 220 cows from two leukosis herds and 25 cows from leukosis free control herd. Trypanosome incidences were determined during summers of 1969 and 1970 by inoculating whole blood onto blood agar slants and incubating at room temperature. Incidence of trypanosomiasis in cattle was found to be variable, possibly due to factors affecting the primary isolation of Trypanosoma theileri. A small trypanosome resembling Trypanosoma uniforme was found occasionally as a concomitant infection with T. theileri. Trypanosomiasis occurred with equal frequency in the animals of the leukosis and the control herds. No correlations were noted between trypanosomiasis, lymphocytosis and DNA synthesizing lymphocytes in peripheral circulation. (+info)
Suppression of antibody response to Leptospira biflexa and Brucella abortus and recovery from immunosuppression after Berenil treatment.
(4/68)
Zebu cattle infected with either Trypanosoma congolense EATRO 1800 or Trypanosoma vivax EATRO 1721 had suppressed humoral immune responses to Leptospira biflexa injected intravenously and to attenuated Brucella abortus injected subcutaneously. T. congolense infections were more suppressive than T. vivax infections. In cattle infected with T. vivax, the suppression of immune responses to both bacterial immunogens was abrogated when the animals were treated with Berenil at the time of antigen administration. In cattle infected with T. congolense, simultaneous Berenil treatment at the time of vaccination abolished the suppression of immune response to L. biflexa, and lessened but did not abrogate the suppression of immune response to B. abortus. (+info)
Serial analysis of gene expression (SAGE) in bovine trypanotolerance: preliminary results.
(5/68)
In Africa, trypanosomosis is a tsetse-transmitted disease which represents the most important constraint to livestock production. Several indigenous West African taurine Bos taurus) breeds, such as the Longhorn (N'Dama) cattle are well known to control trypanosome infections. This genetic ability named "trypanotolerance" results from various biological mechanisms under multigenic control. The methodologies used so far have not succeeded in identifying the complete pool of genes involved in trypanotolerance. New post genomic biotechnologies such as transcriptome analyses are efficient in characterising the pool of genes involved in the expression of specific biological functions. We used the serial analysis of gene expression (SAGE) technique to construct, from Peripheral Blood Mononuclear Cells of an N'Dama cow, 2 total mRNA transcript libraries, at day 0 of a Trypanosoma congolense experimental infection and at day 10 post-infection, corresponding to the peak of parasitaemia. Bioinformatic comparisons in the bovine genomic databases allowed the identification of 187 up- and down- regulated genes, EST and unknown functional genes. Identification of the genes involved in trypanotolerance will allow to set up specific microarray sets for further metabolic and pharmacological studies and to design field marker-assisted selection by introgression programmes. (+info)
A light and electron microscopic study of changes in blood and bone marrow in acute hemorrhagic Trypanosoma vivax infection in calves.
(6/68)
Eleven 6-month-old calves were tsetse fly challenged with a stock of Trypanosoma vivax (IL 2337) that causes hemorrhagic infection. The calves were randomly euthanatized every 4 to 6 days; two other calves served as controls. Peripheral blood changes included anemia, thrombocytopenia, and an initial leukopenia. Later in the course of infection, leukocytosis associated with lymphocytosis and neutropenia developed. Moderate reticulocytosis (highest mean count 3.6 +/- 3.7%, maximum count 9.4%) accompanied the first wave of parasitemia, but poor response (highest mean 0.4 +/- 0.0%) occurred during the second wave, despite the persistence of severe anemia. Light microscopic examination of bone marrow samples showed a drop in the myeloid: erythroid ratio with a decrease in granulocytes, particularly metamyelocytes, bands, and segmenters. Increase in lymphocyte counts corresponded with the appearance of lymphoid nodules within the marrow. Megakaryocytic volume increased significantly in infected animals, and some megakaryocytes showed emperipolesis of red cells, neutrophils, and lymphocytes. Transmission electron microscopic examination of the bone marrow revealed that trypanosomes had crossed the sinusoidal endothelium into the hematopoietic compartment as early as the second day of parasitemia. Macrophages proliferated in the bone marrow; and from the second day of parasitemia until the end of the experimental infection, on day 46, the macrophages had phagocytosed normoblasts, eosinophil and neutrophil myelocytes, metamyelocytes, bands, and segmenters, as well as reticulocytes, erythrocytes, and thrombocytes. Therefore, dyserythropoiesis and dysgranulocytopoiesis were responsible, in part, for the observed anemia and granulocytopenia, respectively. (+info)
Parasite-specific T-cell responses of trypanotolerant and trypanosusceptible cattle during infection with Trypanosoma congolense.
(7/68)
During primary tsetse-transmitted challenge of Boran (Bos indicus) cattle with Trypanosoma congolense ILNat 3.1, a transient parasite antigen-specific T-cell proliferative response was observed in peripheral blood mononuclear cells and splenic mononuclear cells stimulated in vitro. A response was also observed with cells of N'Dama (Bos taurus) cattle, but in this case higher stimulation indices were observed and the response was maintained until the termination of the experiment at 40 days post-infection (p.i.). The highest parasite antigen-specific proliferative responses were observed at 20 days post-infection. At this time N'Dama cattle not only responded to the antigens derived from the infecting clone (ILNat 3.1), but also to antigens from a clone of a different serodeme (ILNaR 2), whereas Boran cattle only recognized antigens from the infecting clone of parasites. To determine the molecular mass of the antigenic trypanosome proteins, whole trypanosome lysates made from T. congolense ILNat 3.1 were fractionated by SDS-PAGE and transferred onto nitrocellulose membranes. The major protein bands were isolated and used directly in T-cell proliferation assays. In this instance, no differences in the antigen recognition profiles of Boran and N'Dama cattle were observed. The variable surface glycoprotein did not induce T-cell proliferation in infected cattle despite the presence of serum antibodies to this variable antigenic type. (+info)
Cytokine mRNA profiling of peripheral blood mononuclear cells from trypanotolerant and trypanosusceptible cattle infected with Trypanosoma congolense.
(8/68)
To examine differences in cytokine profiles that may confer tolerance/susceptibility to bovine African trypanosomiasis, N'Dama (trypanotolerant, n = 8) and Boran (trypanosusceptible, n = 8) cattle were experimentally challenged with Trypanosoma congolense. Blood samples were collected over a 34-day period, and RNA was extracted from peripheral blood mononuclear cells. The expression levels of a panel of 14 cytokines were profiled over the time course of infection and between breeds. Messenger RNA (mRNA) transcript levels for the IL2, IL8, and IL1RN genes were significantly downregulated across the time course of infection in both breeds. There was an early increase in transcripts for genes encoding proinflammatory mediators (IFNG, IL1A, TNF, and IL12) in N'Dama by 14 days postinfection (dpi) compared with preinfection levels that was not detected in the susceptible Boran breed. By the time of peak parasitemia, a type 2 helper T cells (T(H)2)-like cytokine environment was prevalent that was particularly evident in the Boran. Increases in transcripts for the IL6 (29 and 34 dpi) and IL10 (21, 25, and 29 dpi) genes were detected that were higher in the Boran compared with N'Dama. These findings highlight the implications for using murine models to study the bovine immune response to trypanosomiasis, where in some cases cytokine expression patterns differ. Overall, these data suggest that the trypanotolerant N'Dama are more capable of responding very early in infection with proinflammatory and T(H)1 type cytokines than the trypanosusceptible Boran and may explain why N'Dama control parasitemia more efficiently than Boran during the early stages of infection. (+info)