Limits...
Mechanisms controlling anaemia in Trypanosoma congolense infected mice.

Noyes HA, Alimohammadian MH, Agaba M, Brass A, Fuchs H, Gailus-Durner V, Hulme H, Iraqi F, Kemp S, Rathkolb B, Wolf E, de Angelis MH, Roshandel D, Naessens J - PLoS ONE (2009)

Bottom Line: Furthermore, functional T lymphocytes are not required for the induction of anaemia, since suppression of T cell activity with Cyclosporin A had neither an effect on the course of infection nor on anaemia.However, the expression of transcription factors and genes involved in erythropoiesis and haemolysis did correlate with the expression of the inflammatory cytokines Il6 and Ifng.The innate immune response appears to be the major contributor to the inflammation associated with anaemia since suppression of T cells with CsA had no observable effect.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, University of Liverpool, Liverpool, United Kingdom.

ABSTRACT

Background: Trypanosoma congolense are extracellular protozoan parasites of the blood stream of artiodactyls and are one of the main constraints on cattle production in Africa. In cattle, anaemia is the key feature of disease and persists after parasitaemia has declined to low or undetectable levels, but treatment to clear the parasites usually resolves the anaemia.

Methodology/principal findings: The progress of anaemia after Trypanosoma congolense infection was followed in three mouse strains. Anaemia developed rapidly in all three strains until the peak of the first wave of parasitaemia. This was followed by a second phase, characterized by slower progress to severe anaemia in C57BL/6, by slow recovery in surviving A/J and a rapid recovery in BALB/c. There was no association between parasitaemia and severity of anaemia. Furthermore, functional T lymphocytes are not required for the induction of anaemia, since suppression of T cell activity with Cyclosporin A had neither an effect on the course of infection nor on anaemia. Expression of genes involved in erythropoiesis and iron metabolism was followed in spleen, liver and kidney tissues in the three strains of mice using microarrays. There was no evidence for a response to erythropoietin, consistent with anaemia of chronic disease, which is erythropoietin insensitive. However, the expression of transcription factors and genes involved in erythropoiesis and haemolysis did correlate with the expression of the inflammatory cytokines Il6 and Ifng.

Conclusions/significance: The innate immune response appears to be the major contributor to the inflammation associated with anaemia since suppression of T cells with CsA had no observable effect. Several transcription factors regulating haematopoiesis, Tal1, Gata1, Zfpm1 and Klf1 were expressed at consistently lower levels in C57BL/6 mice suggesting that these mice have a lower haematopoietic capacity and therefore less ability to recover from haemolysis induced anaemia after infection.

Show MeSH

Related in: MedlinePlus

Expression of genes involved in iron recycling in the liver.Hamp is a negative regulator of Slc40a1, which exports iron from macrophages. Despite a decline in Hamp expression at day 17 there was no corresponding increase in Slc40a1. Cd163 and Slc11a1 are involved in uptake by macrophages of haem and molecular iron from the plasma. Both responded strongly to infection but the increase in Slc11a1 may be for acquisition of iron for generation of oxidative stress for parasite killing rather than iron recycling.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2664899&req=5

pone-0005170-g012: Expression of genes involved in iron recycling in the liver.Hamp is a negative regulator of Slc40a1, which exports iron from macrophages. Despite a decline in Hamp expression at day 17 there was no corresponding increase in Slc40a1. Cd163 and Slc11a1 are involved in uptake by macrophages of haem and molecular iron from the plasma. Both responded strongly to infection but the increase in Slc11a1 may be for acquisition of iron for generation of oxidative stress for parasite killing rather than iron recycling.

Mentions: Il6 expression in the liver did not change (not shown). Hamp expression increased slightly post infection in all strains before declining to below baseline levels at day 17 (Fig. 12). Slc40a1 expression in the liver followed that of Hamp (Fig. 12) and declined steadily in the spleen (Not shown). After export by SLC40A1, iron is loaded onto transferrin by Hephaestin, the expression of which remained constant until day 9 (Not shown). These data provide no persuasive evidence for substantial change in iron recycling after infection despite the evidence for a >10 fold increase in macrophage numbers. The relatively steady state expression of iron recycling genes compared with the large increase in expression of macrophage associated genes suggests that iron recycling by individual cells may have declined substantially.


Mechanisms controlling anaemia in Trypanosoma congolense infected mice.

Noyes HA, Alimohammadian MH, Agaba M, Brass A, Fuchs H, Gailus-Durner V, Hulme H, Iraqi F, Kemp S, Rathkolb B, Wolf E, de Angelis MH, Roshandel D, Naessens J - PLoS ONE (2009)

Expression of genes involved in iron recycling in the liver.Hamp is a negative regulator of Slc40a1, which exports iron from macrophages. Despite a decline in Hamp expression at day 17 there was no corresponding increase in Slc40a1. Cd163 and Slc11a1 are involved in uptake by macrophages of haem and molecular iron from the plasma. Both responded strongly to infection but the increase in Slc11a1 may be for acquisition of iron for generation of oxidative stress for parasite killing rather than iron recycling.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2664899&req=5

pone-0005170-g012: Expression of genes involved in iron recycling in the liver.Hamp is a negative regulator of Slc40a1, which exports iron from macrophages. Despite a decline in Hamp expression at day 17 there was no corresponding increase in Slc40a1. Cd163 and Slc11a1 are involved in uptake by macrophages of haem and molecular iron from the plasma. Both responded strongly to infection but the increase in Slc11a1 may be for acquisition of iron for generation of oxidative stress for parasite killing rather than iron recycling.
Mentions: Il6 expression in the liver did not change (not shown). Hamp expression increased slightly post infection in all strains before declining to below baseline levels at day 17 (Fig. 12). Slc40a1 expression in the liver followed that of Hamp (Fig. 12) and declined steadily in the spleen (Not shown). After export by SLC40A1, iron is loaded onto transferrin by Hephaestin, the expression of which remained constant until day 9 (Not shown). These data provide no persuasive evidence for substantial change in iron recycling after infection despite the evidence for a >10 fold increase in macrophage numbers. The relatively steady state expression of iron recycling genes compared with the large increase in expression of macrophage associated genes suggests that iron recycling by individual cells may have declined substantially.

Bottom Line: Furthermore, functional T lymphocytes are not required for the induction of anaemia, since suppression of T cell activity with Cyclosporin A had neither an effect on the course of infection nor on anaemia.However, the expression of transcription factors and genes involved in erythropoiesis and haemolysis did correlate with the expression of the inflammatory cytokines Il6 and Ifng.The innate immune response appears to be the major contributor to the inflammation associated with anaemia since suppression of T cells with CsA had no observable effect.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, University of Liverpool, Liverpool, United Kingdom.

ABSTRACT

Background: Trypanosoma congolense are extracellular protozoan parasites of the blood stream of artiodactyls and are one of the main constraints on cattle production in Africa. In cattle, anaemia is the key feature of disease and persists after parasitaemia has declined to low or undetectable levels, but treatment to clear the parasites usually resolves the anaemia.

Methodology/principal findings: The progress of anaemia after Trypanosoma congolense infection was followed in three mouse strains. Anaemia developed rapidly in all three strains until the peak of the first wave of parasitaemia. This was followed by a second phase, characterized by slower progress to severe anaemia in C57BL/6, by slow recovery in surviving A/J and a rapid recovery in BALB/c. There was no association between parasitaemia and severity of anaemia. Furthermore, functional T lymphocytes are not required for the induction of anaemia, since suppression of T cell activity with Cyclosporin A had neither an effect on the course of infection nor on anaemia. Expression of genes involved in erythropoiesis and iron metabolism was followed in spleen, liver and kidney tissues in the three strains of mice using microarrays. There was no evidence for a response to erythropoietin, consistent with anaemia of chronic disease, which is erythropoietin insensitive. However, the expression of transcription factors and genes involved in erythropoiesis and haemolysis did correlate with the expression of the inflammatory cytokines Il6 and Ifng.

Conclusions/significance: The innate immune response appears to be the major contributor to the inflammation associated with anaemia since suppression of T cells with CsA had no observable effect. Several transcription factors regulating haematopoiesis, Tal1, Gata1, Zfpm1 and Klf1 were expressed at consistently lower levels in C57BL/6 mice suggesting that these mice have a lower haematopoietic capacity and therefore less ability to recover from haemolysis induced anaemia after infection.

Show MeSH
Related in: MedlinePlus