Immune depression in bovine trypanosomiasis: effects of acute and chronic Trypanosoma congolense and chronic Trypanosoma vivax infections on antibody response to Brucella abortus vaccine

Rurangirwa, Fred R.; Musoke, A.J.; Nantulya, V.M.; Tabel, H.

doi:10.1111/j.1365-3024.1983.tb00743.x

Cited by 50 publications

(23 citation statements)

References 24 publications

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“…Similar observations have been made in domestic animals, where the antibody response to and/or efficacy of vaccination against e.g. contagious bovine pleuropneumonia [35], foot and mouth disease [36], swine fever [37], antrax spore [38] and Brucella abortus [39] were affected when given during infection with various animal trypanosomes. Moreover, in the immunized T.b.…”

Section: Discussionsupporting

confidence: 73%

Gambiense Human African Trypanosomiasis and Immunological Memory: Effect on Phenotypic Lymphocyte Profiles and Humoral Immunity

et al. 2014

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In mice, experimental infection with Trypanosoma brucei causes decreased bone marrow B-cell development, abolished splenic B-cell maturation and loss of antibody mediated protection including vaccine induced memory responses. Nothing is known about this phenomenon in human African trypanosomiasis (HAT), but if occurring, it would imply the need of revaccination of HAT patients after therapy and abolish hope for a HAT vaccine. The effect of gambiense HAT on peripheral blood memory T- and B-cells and on innate and vaccine induced antibody levels was examined. The percentage of memory B- and T-cells was quantified in peripheral blood, prospectively collected in DR Congo from 117 Trypanosoma brucei gambiense infected HAT patients before and six months after treatment and 117 controls at the same time points. Antibodies against carbohydrate antigens on red blood cells and against measles were quantified. Before treatment, significantly higher percentages of memory B-cells, mainly T-independent memory B-cells, were observed in HAT patients compared to controls (CD20+CD27+IgM+, 13.0% versus 2.0%, p<0.001). The percentage of memory T-cells, mainly early effector/memory T-cells, was higher in HAT (CD3+CD45RO+CD27+, 19.4% versus 16.7%, p = 0.003). After treatment, the percentage of memory T-cells normalized, the percentage of memory B-cells did not. The median anti-red blood cell carbohydrate IgM level was one titer lower in HAT patients than in controls (p<0.004), and partially normalized after treatment. Anti-measles antibody concentrations were lower in HAT patients than in controls (medians of 1500 versus 2250 mIU/ml, p = 0.02), and remained so after treatment, but were above the cut-off level assumed to provide protection in 94.8% of HAT patients, before and after treatment (versus 98.3% of controls, p = 0.3). Although functionality of the B-cells was not verified, the results suggest that immunity was conserved in T.b. gambiense infected HAT patients and that B-cell dysfunction might not be that severe as in mouse models.

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Section: Discussionsupporting

confidence: 73%

Gambiense Human African Trypanosomiasis and Immunological Memory: Effect on Phenotypic Lymphocyte Profiles and Humoral Immunity

et al. 2014

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“…Generalized immunosuppression is a prominent feature of both natural (cattle) and experimental (mice) African trypanosomiasis [35], [36], [37]. However, the exact mechanism through which African trypanosomes induce immunosuppression is still not well defined.…”

Section: Discussionmentioning

confidence: 99%

Regulatory T Cells Enhance Susceptibility to Experimental Trypanosoma Congolense Infection Independent of Mouse Genetic Background

et al. 2012

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BackgroundBALB/c mice are highly susceptible while C57BL/6 are relatively resistant to experimental Trypanosoma congolense infection. Although regulatory T cells (Tregs) have been shown to regulate the pathogenesis of experimental T. congolense infection, their exact role remains controversial. We wished to determine whether Tregs contribute to distinct phenotypic outcomes in BALB/c and C57BL/6 mice and if so how they operate with respect to control of parasitemia and production of disease-exacerbating proinflammatory cytokines.Methodology/FindingsBALB/c and C57BL/6 mice were infected intraperitoneally (i.p) with 103 T. congolense clone TC13 and both the kinetics of Tregs expansion and intracellular cytokine profiles in the spleens and livers were monitored directly ex vivo by flow cytometry. In some experiments, mice were injected with anti-CD25 mAb prior or post T. congolense infection or adoptively (by intravenous route) given highly enriched naïve CD25+ T lymphocytes prior to T. congolense infection and the inflammatory cytokine/chemokine levels and survival were monitored. In contrast to a transient and non significant increase in the percentages and absolute numbers of CD4+CD25+Foxp3+ T cells (Tregs) in C57BL/6 mouse spleens and livers, a significant increase in the percentage and absolute numbers of Tregs was observed in spleens of infected BALB/c mice. Ablation or increasing the number of CD25+ cells in the relatively resistant C57BL/6 mice by anti-CD25 mAb treatment or by adoptive transfer of CD25+ T cells, respectively, ameliorates or exacerbates parasitemia and production of proinflammatory cytokines.ConclusionCollectively, our results show that regulatory T cells contribute to susceptibility in experimental murine trypanosomiasis in both the highly susceptible BALB/c and relatively resistant C57BL/6 mice.

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“…In this context it is remarkable to note that studies performed 3 decades ago already indicated that T. brucei infections abrogate B cell memory responses to thymus-dependent and thymus-independent antigens using DNP-KLH and DNP-Ficoll as antigens for vaccination [29]. Additionally, earlier investigations in domestic animals showed that infections with African trypanosomes abrogate the efficacy of several commercial vaccines against the foot and mouth disease, swine fever, anthrax spores, Brucella abortis and louping-ill vaccine [43],[44],[45],[46],[47]. However, till now no attention has been given to the consequences of T. brucei infections on the immune response induced by commercially available human vaccines.…”

Section: Discussionmentioning

confidence: 99%

Trypanosomiasis-Induced B Cell Apoptosis Results in Loss of Protective Anti-Parasite Antibody Responses and Abolishment of Vaccine-Induced Memory Responses

et al. 2008

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African trypanosomes of the Trypanosoma brucei species are extra-cellular parasites that cause human African trypanosomiasis (HAT) as well as infections in game animals and livestock. Trypanosomes are known to evade the immune response of their mammalian host by continuous antigenic variation of their surface coat. Here, we aim to demonstrate that in addition, trypanosomes (i) cause the loss of various B cell populations, (ii) disable the hosts' capacity to raise a long-lasting specific protective anti-parasite antibody response, and (iii) abrogate vaccine-induced protective response to a non-related human pathogen such as Bordetella pertussis. Using a mouse model for T. brucei, various B cell populations were analyzed by FACS at different time points of infection. The results show that during early onset of a T. brucei infection, spleen remodeling results in the rapid loss of the IgM+ marginal zone (IgM+MZ) B cell population characterized as B220+IgMHighIgDInt CD21HighCD23LowCD1d+CD138−. These cells, when isolated during the first peak of infection, stained positive for Annexin V and had increased caspase-3 enzyme activity. Elevated caspase-3 mRNA levels coincided with decreased mRNA levels of the anti-apoptotic Bcl-2 protein and BAFF receptor (BAFF-R), indicating the onset of apoptosis. Moreover, affected B cells became unresponsive to stimulation by BCR cross-linking with anti-IgM Fab fragments. In vivo, infection-induced loss of IgM+ B cells coincided with the disappearance of protective variant-specific T-independent IgM responses, rendering the host rapidly susceptible to re-challenge with previously encountered parasites. Finally, using the well-established human diphtheria, tetanus, and B. pertussis (DTPa) vaccination model in mice, we show that T. brucei infections abrogate vaccine-induced protective responses to a non-related pathogen such as B. pertussis. Infections with T. brucei parasites result in the rapid loss of T–cell independent IgM+MZ B cells that are normally functioning as the primary immune barrier against blood-borne pathogens. In addition, ongoing trypanosome infections results in the rapid loss of B cell responsiveness and prevent the induction of protective memory responses. Finally, trypanosome infections disable the host's capacity to recall vaccine-induced memory responses against non-related pathogens. In particular, these last results call for detailed studies of the effect of HAT on memory recall responses in humans, prior to the planning of any mass vaccination campaign in HAT endemic areas.

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Immune depression in bovine trypanosomiasis: effects of acute and chronic Trypanosoma congolense and chronic Trypanosoma vivax infections on antibody response to Brucella abortus vaccine

Cited by 50 publications

References 24 publications

Gambiense Human African Trypanosomiasis and Immunological Memory: Effect on Phenotypic Lymphocyte Profiles and Humoral Immunity

Gambiense Human African Trypanosomiasis and Immunological Memory: Effect on Phenotypic Lymphocyte Profiles and Humoral Immunity

Regulatory T Cells Enhance Susceptibility to Experimental Trypanosoma Congolense Infection Independent of Mouse Genetic Background

Trypanosomiasis-Induced B Cell Apoptosis Results in Loss of Protective Anti-Parasite Antibody Responses and Abolishment of Vaccine-Induced Memory Responses

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