Neither of these genes appeared to respond to infection or to be differentially expressed, although Ptp4a1 selleck chemicals was highly expressed throughout the infection (not shown). Other Epo responsive genes did appear to respond to infection: Eif1a (Eukaryotic translation initiation factor) and Kif3a (kinesin family member 3A) were up regulated in all three mouse strains at day 7 and 9 respectively (Fig 6). However, since these genes participate in multiple signal transduction pathways, their up-regulation may be related to inflammation rather than erythropoiesis [32]. Figure 6 EPO responsive genes. Erythropoietin primarily acts through the erythropoietin receptor (Epor) that is exclusively expressed on cells from the erythroid lineage. So the level of expression of Epor may be related to the number of erythroid cells in the tissues.

In uninfected mice, Epor transcription was highest in A/J mice. After infection C57BL/6 mice tended to have lower levels of expression than either A/J or BALB/c mice although this was only significant if the expression levels were compared over the whole time course (p=0.00003 with respect to BALB/c mice and p=0.043 with respect to A/J mice). This was consistent with lower erythropoiesis and haemoglobin titre in C57BL/6 mice. However, given the small difference in expression and the lack of evidence for changes in Epo response genes this may not be an important mechanism driving anaemia after T. congolense infection. Interferon gamma (Ifng) down regulates Kit ligand (Kitl) and Epor and may be an important contributor to anaemia of infection [33].

Kit (CD117) is a receptor for Kitl (SCF or Stem Cell Factor), which acts synergistically with Epo in the promotion of erythropoeisis [33]. Ifng expression Batimastat increased approximately 8-fold after infection in all mouse strains and then declined fastest in BALB/c and remained highest in C57BL/6 consistent with the observed haemoglobin titres (Fig 7). Consistent with the inhibitory activity of IFN-��, the expression of Kit and Epor all declined somewhat at day 7 pi and C57BL/6 had the lowest levels of expression after day three (Fig 7). Higher levels of Kitl may be indicative of higher levels of erythropoiesis. In the spleen Kitl expression was highest in A/J and lowest in C57BL/6 from day 3 to 9 (Fig 7). Figure 7 Genes that mediate haematopoiesis. Insulin like growth factor (Igf1) appears to be more important than Epo for regulation of erythropoiesis in some anaemic patients [34], [35], [36]. Expression of Igf1 declined in C57BL/6 mice till day 7 pi, while it increased in A/J mice and was more than twice as high as in C57BL/6 on day 7 (Fig 7). However, differences at other days were small and no correlations with anaemia could be made.