Innate and acquired control of trypanosome parasitaemia in Cape buffalo

Black, Samuel J.; Sicard, E.L; Murphy, Noel B.; Nolan, Derek P.

doi:10.1016/s0020-7519(01)00160-6

Cited by 15 publications

(13 citation statements)

References 16 publications

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“…It is suggested to result in characteristic waves of parasitemia through interplay with anti-VSG-specific antibodies [32]). Interestingly, the presence of VSG switching during in vitro cultivation of trypanosomes under selective drug pressure, demonstrated that antigenic variation can occur in the absence of antibody mediated events [33] .…”

Section: Resultsmentioning

confidence: 99%

The Role of B-cells and IgM Antibodies in Parasitemia, Anemia, and VSG Switching in Trypanosoma brucei–Infected Mice

et al. 2008

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African trypanosomes are extracellular parasitic protozoa, predominantly transmitted by the bite of the haematophagic tsetse fly. The main mechanism considered to mediate parasitemia control in a mammalian host is the continuous interaction between antibodies and the parasite surface, covered by variant-specific surface glycoproteins. Early experimental studies have shown that B-cell responses can be strongly protective but are limited by their VSG-specificity. We have used B-cell (µMT) and IgM-deficient (IgM−/−) mice to investigate the role of B-cells and IgM antibodies in parasitemia control and the in vivo induction of trypanosomiasis-associated anemia. These infection studies revealed that that the initial setting of peak levels of parasitemia in Trypanosoma brucei–infected µMT and IgM−/− mice occurred independent of the presence of B-cells. However, B-cells helped to periodically reduce circulating parasites levels and were required for long term survival, while IgM antibodies played only a limited role in this process. Infection-associated anemia, hypothesized to be mediated by B-cell responses, was induced during infection in µMT mice as well as in IgM−/− mice, and as such occurred independently from the infection-induced host antibody response. Antigenic variation, the main immune evasion mechanism of African trypanosomes, occurred independently from host antibody responses against the parasite's ever-changing antigenic glycoprotein coat. Collectively, these results demonstrated that in murine experimental T. brucei trypanosomiasis, B-cells were crucial for periodic peak parasitemia clearance, whereas parasite-induced IgM antibodies played only a limited role in the outcome of the infection.

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Section: Resultsmentioning

confidence: 99%

The Role of B-cells and IgM Antibodies in Parasitemia, Anemia, and VSG Switching in Trypanosoma brucei–Infected Mice

et al. 2008

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“…In this context, protective parasite persistence is relevant in African trypanosomiasis as illustrated by trypanosome-infected Cape buffalo which exhibit lowlevel infection and resistance to clinical complications and re-infection [109,110]. Hence, this type of immune intervention represents an alternative to situations where conventional vaccination fails and where eradication of the reservoir, underlying the problem of constant population re-infection, cannot be envisaged.…”

Section: Discussionmentioning

confidence: 99%

The Central Role of Macrophages in Trypanosomiasis-Associated Anemia:Rationale for Therapeutical Approaches

Stijlemans¹,

Vankrunkelsven²,

Caljon³

et al. 2010

EMIDDT

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Bovine African trypanosomiasis causes severe economical problems on the African continent and one of the most prominent immunopathological parameters associated with this parasitic infection is anemia. In this report we review the current knowledge of the mechanisms underlying trypanosomiasis-associated anemia. In first instance, the central role of macrophages and particularly their activation state in determining the outcome of the disease (i.e. trypanosusceptibility versus trypanotolerance) will be discussed. In essence, while persistence of classically activated macrophages (M1) contributes to anemia development, switching towards alternatively activated macrophages (M2) alleviates pathology including anemia. Secondly, while parasite-derived glycolipids such as the glycosylphosphatidylinositol (GPI) induce M1, host-derived IL-10 blocks M1-mediated inflammation, promotes M2 development and prevents anemia development. In this context, strategies aimed at inducing the M1 to M2 switch, such as GPI-based treatment, adenoviral delivery of IL-10 and induction of IL-10 producing regulatory T cells will be discussed. Finally, the crucial role of iron-homeostasis in trypanosomiasis-associated anemia development will be documented to stress the analogy with anemia of chronic disease (ACD), hereby providing new insight that might contribute to the treatment of ACD.

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“…Our investigation of trypanosome control in Cape buffaloes revealed a novel extracellular XO-dependent oxidative defense that contributes to control of the acute phase of parasitemia, but is not responsible for the longterm, stable suppression of parasitemia in these hosts (9,80). An interesting aspect of the defense system is the infection-induced transitory decline in erythrocyte-associated and serum catalase.…”

Section: Discussionmentioning

confidence: 99%

“…The restoration of blood catalase to its preinfection level is accompanied by repopulation of the blood with trypanosomes (Table 1), presumably from another niche, such as the lymph or interstitial fluids, and the onset of the cryptic phase of infection, which is characterized by the sustained presence of 1-20 mouse-infective (66) and tissue culture growth-competent (Table 1) parasites/ml of blood. Our ongoing studies suggest that an acquired immune response involving antibodies reactive with trypanosome growth factor receptors may control the organisms at this stage of infection (9).…”

Section: Concluding Commentsmentioning

confidence: 99%

Serum Xanthine Oxidase: Origin, Regulation, and Contribution to Control of Trypanosome Parasitemia

Wang

Praagh

Hamilton

et al. 2002

Antioxidants & Redox Signaling

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African trypanosomiasis is caused by Salivarian trypanosomes, tsetse fly-transmitted protozoa that inhabit the blood plasma, lymph and interstitial fluids, and, in the case of Trypanosoma brucei species, also the cerebrospinal fluid of mammal hosts. Trypanosomiasis in people and domestic animals manifests as recurring waves of parasites in the blood and is typically fatal. In contrast, trypanosomiasis in Cape buffaloes, which are naturally selected to resist the disease, is characterized by the development of only one or a few waves of parasitemia, after which the infection becomes cryptic, being maintained by the presence of 1-20 mammal-infective organisms/ml of blood. The control of the acute phase of parasitemia in Cape buffaloes correlates with a decline in blood catalase activity and the generation of trypanocidal H(2)O(2) in serum during the catabolism of endogenous purine by xanthine oxidase. Here we review features of this response, and of trypanosome metabolism, that facilitate H(2)O(2)-mediated killing of the parasites with minimal damage to the host. We also discuss the origin and regulation of serum xanthine oxidase and catalase, and show how recovery of serum catalase in infected Cape buffaloes precludes a role for H(2)O(2) in the long-term, stable suppression of trypanosome parasitemia.

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Innate and acquired control of trypanosome parasitaemia in Cape buffalo

Cited by 15 publications

References 16 publications

The Role of B-cells and IgM Antibodies in Parasitemia, Anemia, and VSG Switching in Trypanosoma brucei–Infected Mice

The Role of B-cells and IgM Antibodies in Parasitemia, Anemia, and VSG Switching in Trypanosoma brucei–Infected Mice

The Central Role of Macrophages in Trypanosomiasis-Associated Anemia:Rationale for Therapeutical Approaches

Serum Xanthine Oxidase: Origin, Regulation, and Contribution to Control of Trypanosome Parasitemia

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