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J.V. Neves et al.
ABCD
EFGH
IJKL
MNOP
QRS
Figure 3. Gene expression in the liver, spleen, kidney and bone marrow after experimental infection of BALB/c mice with T.b. brucei. Relative mRNA expression of several genes was measured 1, 4, 7, 14, and 21 days post infection, by real-time polymerase chain reaction. Liver (A) Hamp1, (B) Fpn1, (C) Tf, (D) Fth1; spleen (E) Hamp1, (F) Fpn1, (G) Fth1, (H) Hbb, (I) Epor, (J) Erfe, (K) Twsg1; kidney (L) Hamp1, (M) Epo; bone marrow (N) Hamp1, (O) Hbb, (P) Epor, (Q) Erfe, (R) Gdf15, (S) Twsg1. Values are represented as mean±standard deviation (n=5). Differences from the control groups were considered significant at *P<0.05, **P<0.01, and ***P<0.001.
was observed starting day 1, peaking at day 4, and return- ing to control levels at day 7 (Figure 3L). Levels of Epo were up-regulated throughout the duration of the experi- ment (Figure 3M).
Finally, in the BM, Hamp1 expression was found to be increased as early as day 1, followed by a gradual down- regulation up to day 7, and a recovery to normal values towards day 21 (Figure 3N). For Hbb, Epor and Erfe, a sim- ilar pattern of expression was observed, with decreased expression at day 7, followed by gradual increases, and reaching maximum levels at day 21 (Figure 3, panels O-Q). Gdf15 and Twsg1 expressions gradually increased through- out the course of the infection, reaching maximum levels at day 21 (Figure 3R and S).
Hepcidin contributes to the development of anemia in trypanosomal infections
Gene expression profiles indicate that hepcidin might be involved in the development of anemia during trypanoso- mal infection. In order to investigate this, we performed experimental infections in hepcidin deficient (Hamp-/-) mice. No significant differences were found in the parasitemias or total parasite burdens between Hamp-/- and C57BL/6 mice (Online Supplementary Figure S2). Hematologic parameters show development of anemia, with a steady decline of RBC number, hematocrit and hemoglobin levels up to day 7 post infection, followed by a gradual recovery (Figure 4A- D). However, whereas in C57BL/6 mice parameters never fully recover to normal values, in Hamp-/-- mice there is a
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haematologica | 2021; 106(3)