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

Abstract

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.

Contributions of experimental mouse models to the understanding of African trypanosomiasis

“…In T. congolense infections, TNF-deficient mice present severely shortened survival times and fail to control the first parasitaemia peak [14,15,34]. A recent study involving iNOS À/À (inducible nitric oxide synthase-deficient), TNF À/À , TNF-R(receptor)1 À/À and TNF-R2 À/À mice confirmed that TNF and NO cooperate in controlling T. congolense [15].…”

“…brucei and T.b. rhodesiense infection [7,34,41,42]. However, the direct effector function of TNF on trypanosomes is only confirmed in a limited number of T. brucei strains and is not a general operating mechanism [43].…”

Haematological changes in Trypanosoma evansi infected cattle

“…The mean TEC, PCV and Hb reduced significantly (P<0.01) compared to control group, indicating anemia. The patho physiology of anaemia in Trypanosomiasis is complex and multi factorial in origin [7]. It initiates a cascade of events leading to haemolytic anaemia and cardiovascular collapse [8].…”

The Mechanisms of Anaemia in Trypanosomosis: A Review

“…This product is known to lyse red blood cells in the absence of antibodies (in-vitro) and haemodilution (in-vivo). This mechanism has been adequately described in gold fish (Carassius auratus) infected with Trypanosoma dahilewskyi (Nazrul-Islam and Woo, 1991) and in murine models infected with T. b. rhodesiense (Naessens et al, 2005 …”

“…The T. brucei group of trypanosomes (T. brucei, T. b. gambiense, T. b. rhodesianse and T. evansi) mostly invade tissues (humoral) whereas, T. congolense and to a lesser extent T. vivax and T. cruzi predominantly restrict themselves to the blood circulation (haemic) (Igbokwe, 1994;. The mechanism or pathophysiology of anaemia in trypanosomosis is complex and multifactorial in origin (Naessens et al, 2005). It initiates a cascade of events leading to haemolytic anaemia and cardiovascular collapse (Anosa, 1988).…”