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

Benoit      Stijlemans; Ann      Vankrunkelsven; Guy      Caljon; Viki      Bockstal; Martin      Guilliams; Tom      Bosschaerts; Alain      Beschin; Geert      Raes; Stefan      Magez; Patrick   De   Baetselier

doi:10.2174/187153010790827966

Abstract

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.

Keywords: Trypanosomiasis, macrophage activation, iron-homeostasis, erythropoiesis, anemia of inflammation, GPI

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