Role of Cytokines in <i>Trypanosoma brucei</i>-Induced Anaemia: A Review of the Literature

Abstract

BackgroundAnaemia is an important complication of trypanosomiasis. The mechanisms through which trypanosomal infection leads to anaemia are poorly defined. A number of studies have implicated inflammatory cytokines, but these data are limited and inconsistent. In this article, we reviewed the published literature on cytokines associated with Trypanosoma brucei infections and their role in the immunopathology leading to anaemia. MethodologyArticles were searched in PubMed through screening of titles and abstracts with no limitation on date of publishing and study design. Articles in English were searched using keywords "African trypanosomiasis", "sleeping sickness", "Trypanosoma brucei", in all possible combinations with "anaemia" and/or "cytokines". ResultsTwelve articles examining cytokines and their role in trypanosomeinduced anaemia were identified out of 1095 originally retrieved from PubMed. None of the articles identified were from human-based studies. A total of eight cytokines were implicated, with four cytokines (IFN-γ, IL-10, TNF-α, IL-12) showing an association with anaemia. These articles reported that mice lacking TNF-α were able to control anaemia, and that IFN-γ was linked to severe anaemia given its capacity to suppress erythropoiesis, while IL-10 was shown to regulate IFN-γ and TNF-α, providing a balance that was associated with severity of anaemia. IFN-γ and TNF-α have also been reported to work in concert with other factors such as nitric oxide and iron in order to induce anaemia. ConclusionIFN-γ, IL-10, and TNF-α were the three major cytokines identified to be heavily involved in anaemia caused by Trypanosoma brucei infection. The anti-inflammatory cytokine, IL-10, was shown to counter the effects of proinflammatory cytokines in order to balance the severity of anaemia. The mechanism of anaemia is multifactorial and therefore requires further, more elaborate research. Data from human subjects would also shed more light.

Inflammatory and Pro-resolving Lipids in Trypanosomatid Infections: A Key to Understanding Parasite Control

“…In this respect, the regulatory cytokine IL-10 is induced by the parasite, decreasing the levels of NO• and TNF-α in infected mice, reducing organ damage, and favoring host survival ( Guilliams et al, 2009 ). Also, results from several animal studies indicate that T. brucei -induced IL-10 production counters anemia; thus, this cytokine may play a crucial role in parasite and host survival ( Musaya et al, 2015 ), which concurs with findings from research on human subjects. In the late stage, the levels of IL-10 were found to be elevated irrespective of the geographical location of the patients and the particular genotype of the strain involved in the infection ( Maclean et al, 2004 ).…”

African Trypanosomiasis-Associated Anemia: The Contribution of the Interplay between Parasites and the Mononuclear Phagocyte System

“…Moreover, the prevalence of M1 or M2 during the course of infection correlates with the severity of anemia ( 43 ). Consequently, both pro- and anti-inflammatory cytokines have been shown to be implicated in anemia onset and progression ( 51 ). In this section, different parasite- and host-derived factors contributing to both myeloid cell activation and to acute and chronic anemia development will be discussed.…”

“…However, during the final stage of infection, serum TNF-α reaches the same levels in both LT-α −/− and WT mice, concomitant with similar anemia levels in both mice groups. A possible explanation for this might be that TNF-α is also an important negative regulator of erythropoiesis and this aspect might predominate at later stages of infection ( 51 , 122 ). Hence, strategies to reduce TNF signaling or allowing switching from M1 toward M2 might also be valuable to alleviate chronic anemia development.…”

“…By contrast, IL-10 was shown to positively affect erythropoiesis by downregulating the effects of the pro-inflammatory cytokines ( 145 ). Therefore, the balance between these pro- and anti-inflammatory cytokines during the course of infection determines the course of anemia development ( 51 ). In other words, the ability of the host to mount an efficient erythropoietic response (stress-induced response) to compensate for the enhanced erythrophagocytosis determines whether anemia persists.…”

Immunosuppression in Experimental Chagas Disease Is Mediated by an Alteration of Bone Marrow Stromal Cell Function During the Acute Phase of Infection

“…In addition to this direct infection-induced effect, the hyperinflammation during acute Chagas disease may also lead to reduced viability of stromal cells by apoptosis as is described for cells facing nutritional deprivation (69). A strong mediator of this programmed cell death and subsequent anemia is TNF (70–72). In Chagas disease patients a profound anemia (73) and in some cases an additional thrombocytopenia can occur (74, 75).…”