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Hepcidin and Trypanosoma brucei infection
on the establishment/progression of anemia and the molecular mechanisms involved in iron homeostasis. Furthermore, this study also evaluates the contribution of hepcidin (the key regulator of iron homeostasis19,32) to the anemia established during T.b. brucei infection. Different degrees of anemia severity in trypanosomal infections have been reported and these have been described as being dependent on the host and sub-species causing the infection.3,7 In this study, an early decrease in several hematologic parameters such as the number of RBC and reticulocytes, hematocrit and hemoglobin levels, and an increase in MCV were seen in wild-type (BALB/c and C57BL/6) and in Hamp-/- (gene deficient in C57BL/6 back- ground) mice. This was followed later by an increase in most parameters, never reaching normal levels in wild- type (BALB/c and C57BL/6) animals but fully recovering in Hamp-/- mice.
An in-depth investigation of several erythrocyte popula- tions in the BM of BALB/c mice shows similar patterns in all of them, from the early immature pro-erythroblasts to the late mature polychromatic erythroblasts, most reach- ing the lowest numbers after 7 days of infection, and again followed by gradual recoveries. This was also accompa- nied by late increases in the expression of hemoglobin, in both the spleen and BM.
Iron is essential not only for the host but also for pathogen proliferation, and trypanosome infections are no exception.17,18 In the case of extracellular, blood circulating pathogens, iron is rapidly removed from circulation to pre- vent pathogens from accessing it. This is seen in BALB/c and C57BL/6 mice by the expression profiles of transferrin and ferritin, particularly in the liver, where early increases in both would facilitate iron retention and removal from circulation, as well as by decreases in circulating serum iron and transferrin saturation, and an increase in circulat- ing ferritin.33 This response might be particularly impor- tant in the earliest days of infection, since T. brucei blood- stream forms can acquire iron through pathogen-specific receptors for transferrin and haptoglobin-hemoglobin complexes.34 On the other hand, the higher levels of serum iron and circulating ferritin levels observed in Hamp-/- mice do not appear to influence pathogen proliferation, when compared with the wild-type animals, with parasite levels remaining similar. Although limited data are available regarding extracellular and intracellular parasites, they can both benefit or be suppressed by high iron levels.27,28 This is in contrast with many bacterial infections, where hep- cidin is known to have a crucial role in creating a hypofer- rimic state, to limit iron availability, and protect the host both against infections caused by siderophilic bacteria23,35
Figure 8. Schematic representation of the mechanisms of hepcidin regulation during the development and recovery from anemia in T.b. brucei infections.
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