Role of iron homeostasis in trypanosomiasis-associated anemia.

TitleRole of iron homeostasis in trypanosomiasis-associated anemia.
Publication TypeJournal Article
Year of Publication2008
AuthorsStijlemans, B., A. Vankrunkelsven, L. Brys, S. Magez, and P. De Baetselier
Date Published2008
Type of Articleparasites
KeywordsAcute Disease, Anemia, Animals, Cation Transport Proteins, Ceruloplasmin, Chronic Disease, Cytokines, Disease Models, Animal, Erythrocytes, Female, Gene Expression Regulation, Homeostasis, Iron, Macrophages, Mice, Mice, Inbred C57BL, Phagocytosis, Transferrin, Trypanosoma brucei brucei, Trypanosomiasis, African

Anemia is a well-established infection-associated immunopathological feature of trypanosomiasis and the degree of the anemia is a reliable indicator of the severity of infection. Since infections with trypanosomes triggers a strong cytokine production and a type I immune response, the trypanosome-elicited anemia may be type I cytokine driven. This type of anemia termed anemia of chronic disease is characterized by an imbalance between erythrophagocytosis and erythropoiesis that is linked to a perturbed iron homeostasis including altered iron recycling by macrophages and iron sequestration. To further unravel the mechanisms underlying trypanosome-elicited anemia the expression profile of genes involved in erythrophagocytosis, uptake of iron-containing complexes and iron homeostasis was performed during the acute and chronic phase of experimental Trypanosoma brucei infections in a murine model. The results suggest that liver-associated erythrophagocytosis mediated by cytokine-activated macrophages (M1 cells) is the most likely main initiating event of aggressive anemia during the acute phase of infection. Persistence of strong type I cytokine production during the chronic phase of infection leads to hyper-activated M1 cells and a more progressive anemia. RT-PCR analysis of liver tissue demonstrates a strong increase of cell surface receptors involved in uptake of RBC and iron-containing compounds. For genes involved in iron processing we found an increase of ferroportin-1 (FPN-1), transferrin (Tf) and ceruloplasmin (CP) only in the acute phase, suggesting that export of iron is hampered in the chronic phase of infection. Our results suggest that in the chronic phase of trypanosomiasis, the iron-processing pathway is skewed towards iron sequestration, as evidenced by increased ferritin expression, while enhanced uptake of RBC/iron-containing compounds is maintained.

Alternate JournalImmunobiology
PubMed ID18926297