Induction and regulation of<i>Trypanosoma brucei</i>VSG-specific antibody responses

Black, Samuel J.; Guirnalda, Patrick; Frenkel, Deborah; Haynes, Carole; Bockstal, Viki

doi:10.1017/s003118200999165x

Cited by 13 publications

(7 citation statements)

References 47 publications

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“…This is a mechanism of organized surface coat switching that allows these extracellular parasites to continuously escape the host adaptive immune system (12). However, recent data suggest that trypanosomes also actively undermine the adaptive response by causing rapid depletion of the B‐cell compartment (13,14).…”

Section: Mouse Models As a Tool To Study The Humoral Responses Againsmentioning

confidence: 99%

Mouse models for pathogenic African trypanosomes: unravelling the immunology of host–parasite–vector interactions

Magez

Caljon

2011

Parasite Immunology

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African trypanosomiasis is a parasitic disease that affects a variety of mammals, including humans, on the sub-Saharan African continent. To understand the diverse parameters that govern the host-parasite-vector interactions, mouse models for the disease have proven to be a cornerstone. Despite the fact that most trypanosomes cannot be considered natural pathogens for rodents, experimental infections in mice have shed a tremendous amount of light on the general biology of these parasites and their interaction with and evasion of the mammalian immune system. Different aspects including inflammation, vaccine failure, antigenic variation, resistance/sensitivity to normal human serum and the influence of tsetse compounds on parasite transmission have all been addressed using mouse models. In more recent years, the introduction of various 'knock-out' mouse strains has allowed to analyse the implication of various cytokines, particularly TNF, IFNγ and IL-10, in the regulation of parasitaemia and induction of pathological conditions during infection.

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Section: Mouse Models As a Tool To Study The Humoral Responses Againsmentioning

confidence: 99%

Mouse models for pathogenic African trypanosomes: unravelling the immunology of host–parasite–vector interactions

Magez

Caljon

2011

Parasite Immunology

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“…Indeed, it has been estimated that the VSG density of intact T. brucei parasites is 20 times higher than the density required for BCR cross-linking. So, even if a VSG mosaic coat consists out of two antigenically district variants, each of the variants should in theory be able to mediate regular B cell activation, which is apparently not what happens (60). Yet, experimental infections in distinct mouse strains, as well as their F1 offspring, have shown that susceptibility to infection in terms of limited parasitemia control and shortened survival can be linked to the impaired capacity to mount a proper anti-VSG response.…”

Section: Trypanosomes Avoid Antibody-mediated Killing By Dynamic Surfmentioning

confidence: 99%

Infections With Extracellular Trypanosomes Require Control by Efficient Innate Immune Mechanisms and Can Result in the Destruction of the Mammalian Humoral Immune System

et al. 2020

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Salivarian trypanosomes are extracellular parasites that affect humans, livestock, and game animals around the world. Through co-evolution with the mammalian immune system, trypanosomes have developed defense mechanisms that allow them to thrive in blood, lymphoid vessels, and tissue environments such as the brain, the fat tissue, and testes. Trypanosomes have developed ways to circumvent antibody-mediated killing and block the activation of the lytic arm of the complement pathway. Hence, this makes the innate immune control of the infection a crucial part of the host-parasite interaction, determining infection susceptibility, and parasitemia control. Indeed, trypanosomes use a combination of several independent mechanisms to avoid clearance by the humoral immune system. First, perpetuated antigenic variation of the surface coat allows to escape antibody-mediated elimination. Secondly, when antibodies bind to the coat, they are efficiently transported toward the endocytosis pathway, where they are removed from the coat proteins. Finally, trypanosomes engage in the active destruction of the mammalian humoral immune response. This provides them with a rescue solution in case antigenic variation does not confer total immunological invisibility. Both antigenic variation and B cell destruction pose significant hurdles for the development of anti-trypanosome vaccine strategies. However, developing total immune escape capacity and unlimited growth capabilities within a mammalian host is not beneficial for any parasite, as it will result in the accelerated death of the host itself. Hence, trypanosomes have acquired a system of quorum sensing that results in density-dependent population growth arrest in order to prevent overpopulating the host. The same system could possibly sense the infection-associated host tissue damage resulting from inflammatory innate immune responses, in which case the quorum sensing serves to prevent excessive immunopathology and as such also promotes host survival. In order to put these concepts together, this review summarizes current knowledge on the interaction between Magez et al.Trypanosomosis and Innate Immune Control trypanosomes and the mammalian innate immune system, the mechanisms involved in population growth regulation, antigenic variation and the immuno-destructive effect of trypanosomes on the humoral immune system. Vaccine trials and a discussion on the role of innate immune modulation in these trials are discussed at the end.

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“…False-positive results have been reported in areas of low endemicity [26], and in several foci in West Africa were found some T.b. gambiense strains lacking the gene that encodes the surface glycoprotein LiTat 1.3 [27], main gene targeted by the agglutination process [28, 29]. To solve this problem, in addition to CATT are performed microscopic examinations of lymph aspirated from enlarged cervical lymph nodes or of blood films to assess the presence of the parasite in the lymph or blood [30].…”

Section: Diagnosismentioning

confidence: 99%

“…The emerging challenges for the development of a vaccine against African trypanosomiasis were recently reviewed [29, 110], and in this section, they will be briefly discussed. The cell surface of the procyclic and epimastigote forms of T.b.…”

Section: Treatment and Vaccine Developmentmentioning

confidence: 99%

New Insights in Staging and Chemotherapy of African Trypanosomiasis and Possible Contribution of Medicinal Plants

Etet

Mahomoodally

2012

The Scientific World Journal

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Human African trypanosomiasis (HAT) is a fatal if untreated fly-borne neuroinflammatory disease caused by protozoa of the speciesTrypanosoma brucei(T.b.). The increasing trend of HAT cases has been reversed, but according to WHO experts, new epidemics of this disease could appear. In addition, HAT is still a considerable burden for life quality and economy in 36 sub-Saharan Africa countries with 15–20 million persons at risk. Following joined initiatives of WHO and private partners, the fight against HAT was re-engaged, resulting in considerable breakthrough. We present here what is known at this day about HAT etiology and pathogenesis and the new insights in the development of accurate tools and tests for disease staging and severity monitoring in the field. Also, we elaborate herein the promising progresses made in the development of less toxic and more efficient trypanocidal drugs including the potential of medicinal plants and related alternative drug therapies.

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Induction and regulation ofTrypanosoma bruceiVSG-specific antibody responses

Cited by 13 publications

References 47 publications

Mouse models for pathogenic African trypanosomes: unravelling the immunology of host–parasite–vector interactions

Mouse models for pathogenic African trypanosomes: unravelling the immunology of host–parasite–vector interactions

Infections With Extracellular Trypanosomes Require Control by Efficient Innate Immune Mechanisms and Can Result in the Destruction of the Mammalian Humoral Immune System

New Insights in Staging and Chemotherapy of African Trypanosomiasis and Possible Contribution of Medicinal Plants

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