Tumor necrosis factor alpha plays a key role in the regulation of the experimental infection with Trypanosoma Brucei

Magez, Stefan; Beschin, Alain; Radwanska, Magdalena; Stylemans, B; Favero, H Del; Dijck, Els Van; De, Baetselier Patrick

doi:10.1016/s1383-5769(98)80266-3

Cited by 52 publications

(113 citation statements)

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“…This contrasts with the anaemia associated with malaria [25] and chronic disease [26], which is mediated by TNF-a. In a previous publication [23], it was mentioned that no anaemia was obvious in TNF-a-deficient mice infected with T. brucei brucei. Other signs of pathology were also lacking in the T. brucei-infected TNF-a-knock-out mice: they were as active as uninfected controls and showed no deterioration in their coat condition [23].…”

Section: Discussionmentioning

confidence: 99%

“…In a previous publication [23], it was mentioned that no anaemia was obvious in TNF-a-deficient mice infected with T. brucei brucei. Other signs of pathology were also lacking in the T. brucei-infected TNF-a-knock-out mice: they were as active as uninfected controls and showed no deterioration in their coat condition [23]. In contrast, the coat condition of the T. congolenseinfected TNF-a-deficient mice in our experiments was as poor as that of the infected wild type.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, TNF-adeficient mice have been reported to be highly susceptible to infections with T. congolense , a major parasite of cattle and ruminants, and showed reduced survival rates and higher parasitaemias [21,22]. In a separate study, it was shown that these TNF-a -deficient mice also developed much higher parasitaemias than the wild-type mice when infected with a different trypanosome, T. b. brucei [23], although their survival times were not shorter. These observations suggest that TNF-a plays an important role in parasitaemia control in murine trypanosomiasis, but its contribution to pathogenesis, including anaemia, may be different between T. congolense and T. brucei -infections.…”

Section: Introductionmentioning

confidence: 99%

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TNF-a mediates the development of anaemia in a murine Trypanosoma brucei rhodesiense infection, but not the anaemia associated with a murine Trypanosoma congolense infection

Naessens

Kitani

Nakamura

et al. 2005

Clinical and Experimental Immunology

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SummaryDevelopment of anaemia in inflammatory diseases is cytokine-mediated. Specifically, the levels of tumour necrosis factor-a a a a (TNF-a a a a ), produced by activated macrophages, are correlated with severity of disease and anaemia in infections and chronic disease. In African trypanosomiasis, anaemia develops very early in infection around the time when parasites become detectable in the blood. Since the anaemia persists after the first waves of parasitaemia when low numbers of trypanosomes are circulating in the blood, it is generally assumed that anaemia is not directly induced by a parasite factor, but might be cytokine-mediated, as in other cases of anaemia accompanying inflammation. To clarify the role of TNF-a a a a in the development of anaemia, blood parameters of wild type (TNF-a a a a+ + + + / + + + + ), TNF-a a a a -null (TNF-a a a a -/-) and TNF-a a a a -hemizygous (TNF-a a a a -/ + + + + ) trypanotolerant mice were compared during infections with the cattle parasite Trypanosoma congolense . No differences in PCV, erythrocyte numbers or haemoglobin were observed between TNF-a a a adeficient and wild type mice, suggesting that the decrease in erythrocytes was not mediated by TNF-a a a a . Erythropoetin (EPO) levels increased during infection and no significant differences in EPO levels were observed between the three mouse strains. In contrast, during an infection with the human pathogen Trypanosoma brucei rhodesiense , the number of red blood cells in TNF-a a a adeficient mice remained significantly higher than in the wild type mice. These data suggest that more than one mechanism promotes the development of anaemia associated with trypanosomiasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TNF-a mediates the development of anaemia in a murine Trypanosoma brucei rhodesiense infection, but not the anaemia associated with a murine Trypanosoma congolense infection

Naessens

Kitani

Nakamura

et al. 2005

Clinical and Experimental Immunology

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“…Results showed that TNF-␣ is essential to control parasitemia since PTX-treated fish showed extremely high parasitemia numbers and succumbed faster to the infection. In mice, a crucial role for TNF-␣ in parasitemia control has been described in several studies on African trypanosomes where TNF-␣-deficient mice show severely shortened survival times and fail to control parasitemia (36,81,82). The mechanisms underlining TNF-␣ activity are diverse and parasite species-specific.…”

Section: Discussionmentioning

confidence: 99%

Receptor-Mediated and Lectin-Like Activities of Carp (Cyprinus carpio) TNF-α

Forlenza

Magez²,

Scharsack³

et al. 2009

The Journal of Immunology

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Functional characterization of TNF-α in species other than mammalian vertebrates is limited, and TNF-α has been studied in a limited number of fish species, primarily in vitro using recombinant proteins. Studies on TNF-α from different fish species so far pointed to several inconsistencies, in particular with respect to some receptor-mediated activities of fish TNF-α, such as the ability to directly activate phagocytes. In the present study a comprehensive analysis of in vitro as well as in vivo biological activities of two isoforms of carp TNF-α was performed. Our results show that carp TNF-α directly primes carp phagocytes and indirectly promotes typical receptor-mediated activities such as phagocyte activation by acting via endothelial cells. Additionally, for the first time in nonmammalian vertebrate species, the lectin-like activity of fish TNF-α homologs was investigated. Our results show an evolutionary conservation of function of this receptor-independent activity of TNF-α not only in cyprinid fish, but also in perciform and salmonid fish. The role of TNF-α in vivo, during infections of carp with the blood parasite Trypanoplasma borreli, was examined using three fundamentally different but complementary approaches: (1) inhibition of TNF-α expression, (2) overexpression of TNF-α, and (3) inhibition of shedding of membrane-bound TNF-α. Our results show that, also in fish, a tight regulation of TNF-α expression is important, since depletion or excess of TNF-α can make an important difference to survival of infection. Finally, we demonstrate a crucial protective role for membrane-bound TNF-α, which has a yet unexploited function in fish.

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“…Exposure of macrophages to trypanosome-derived components, including released VSGs, results in an IFN-γ-dependent proinflammatory response that is required to control the initial parasitemia. However, macrophages from chronically infected animals appear to be impaired in their ability to produce proinflammatory cytokines (6)(7)(8). In the case of IL-1β levels, there have been conflicting reports following T. brucei experimental infections, with some studies reporting levels were elevated (9,10), and other studies showing that production of IL-I was severely depressed in infected mice (11).…”

Section: Trypanosoma Bruceimentioning

confidence: 99%

Trypanosoma bruceimetabolite indolepyruvate decreases HIF-1α and glycolysis in macrophages as a mechanism of innate immune evasion

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The parasite Trypanasoma brucei causes African trypanosomiasis, known as sleeping sickness in humans and nagana in domestic animals. These diseases are a major burden in the 36 sub-Saharan African countries where the tsetse fly vector is endemic. Untreated trypanosomiasis is fatal and the current treatments are stagedependent and can be problematic during the meningoencephalitic stage, where no new therapies have been developed in recent years and the current drugs have a low therapeutic index. There is a need for more effective treatments and a better understanding of how these parasites evade the host immune response will help in this regard. The bloodstream form of T. brucei excretes significant amounts of aromatic ketoacids, including indolepyruvate, a transamination product of tryptophan. This study demonstrates that this process is essential in bloodstream forms, is mediated by a specialized isoform of cytoplasmic aminotransferase and, importantly, reveals an immunomodulatory role for indolepyruvate. Indolepyruvate prevents the LPS-induced glycolytic shift in macrophages. This effect is the result of an increase in the hydroxylation and degradation of the transcription factor hypoxia-inducible factor-1α (HIF-1α). The reduction in HIF-1α levels by indolepyruvate, following LPS or trypanosome activation, results in a decrease in production of the proinflammatory cytokine IL-1β. These data demonstrate an important role for indolepyruvate in immune evasion by T. brucei.immunometabolism | innate immunity | immune evasion |

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Tumor necrosis factor alpha plays a key role in the regulation of the experimental infection with Trypanosoma Brucei

Cited by 52 publications

References 0 publications

TNF-a mediates the development of anaemia in a murine Trypanosoma brucei rhodesiense infection, but not the anaemia associated with a murine Trypanosoma congolense infection

TNF-a mediates the development of anaemia in a murine Trypanosoma brucei rhodesiense infection, but not the anaemia associated with a murine Trypanosoma congolense infection

Receptor-Mediated and Lectin-Like Activities of Carp (Cyprinus carpio) TNF-α

Trypanosoma bruceimetabolite indolepyruvate decreases HIF-1α and glycolysis in macrophages as a mechanism of innate immune evasion

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