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

Transcription factors regulating erythropoiesis.Tal1, Gata1, Lmo2, Ldb1, TcfE2a and Zfpm1 (Fog1) form a multimeric DNA binding complex, which regulates primitive haematopoiesis. All six genes were highly expressed and had similar patterns of expression consistent with co-ordinate regulation. Klf1 is involved in erythroid cell proliferation and had similar levels and patterns of expression suggesting that it may be regulated by the same mechanisms. In all cases C57BL/6 mice tended to have the lowest levels of expression after day 3.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2664899&req=5

pone-0005170-g009: Transcription factors regulating erythropoiesis.Tal1, Gata1, Lmo2, Ldb1, TcfE2a and Zfpm1 (Fog1) form a multimeric DNA binding complex, which regulates primitive haematopoiesis. All six genes were highly expressed and had similar patterns of expression consistent with co-ordinate regulation. Klf1 is involved in erythroid cell proliferation and had similar levels and patterns of expression suggesting that it may be regulated by the same mechanisms. In all cases C57BL/6 mice tended to have the lowest levels of expression after day 3.

Mentions: Tal1, Gata1, Lmo2, Ldb1, TcfE2a and Zfpm1 (Fog1) form a multimeric DNA binding complex that regulates primitive haematopoiesis [41]. All six genes were highly expressed, declined in production in the spleen post infection and returned to near baseline levels by day 17, with the exception of Ldb1, Zfpm1 and Tcfe2a in C57BL/6 (Fig 9). The transcription factor EKLF (Klf1) is involved in erythroid cell proliferation and has a similar expression profile suggesting that it might be co-regulated with the other six genes. C57BL/6 had lower levels of Tal1, Gata1, Zfpm1 and Kif1, which are suggestive of lower levels of haematopoiesis in C57BL/6 particularly at later time-points. The similarity of their expression profiles is suggestive of co-ordinate regulation, which is consistent with the requirement for stoichiometric binding of the multimeric complex. The expression of Gata2, which acts earlier in erythropoiesis [41], did not change during infection and did not differ between strains (not shown).


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)

Transcription factors regulating erythropoiesis.Tal1, Gata1, Lmo2, Ldb1, TcfE2a and Zfpm1 (Fog1) form a multimeric DNA binding complex, which regulates primitive haematopoiesis. All six genes were highly expressed and had similar patterns of expression consistent with co-ordinate regulation. Klf1 is involved in erythroid cell proliferation and had similar levels and patterns of expression suggesting that it may be regulated by the same mechanisms. In all cases C57BL/6 mice tended to have the lowest levels of expression after day 3.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0005170-g009: Transcription factors regulating erythropoiesis.Tal1, Gata1, Lmo2, Ldb1, TcfE2a and Zfpm1 (Fog1) form a multimeric DNA binding complex, which regulates primitive haematopoiesis. All six genes were highly expressed and had similar patterns of expression consistent with co-ordinate regulation. Klf1 is involved in erythroid cell proliferation and had similar levels and patterns of expression suggesting that it may be regulated by the same mechanisms. In all cases C57BL/6 mice tended to have the lowest levels of expression after day 3.
Mentions: Tal1, Gata1, Lmo2, Ldb1, TcfE2a and Zfpm1 (Fog1) form a multimeric DNA binding complex that regulates primitive haematopoiesis [41]. All six genes were highly expressed, declined in production in the spleen post infection and returned to near baseline levels by day 17, with the exception of Ldb1, Zfpm1 and Tcfe2a in C57BL/6 (Fig 9). The transcription factor EKLF (Klf1) is involved in erythroid cell proliferation and has a similar expression profile suggesting that it might be co-regulated with the other six genes. C57BL/6 had lower levels of Tal1, Gata1, Zfpm1 and Kif1, which are suggestive of lower levels of haematopoiesis in C57BL/6 particularly at later time-points. The similarity of their expression profiles is suggestive of co-ordinate regulation, which is consistent with the requirement for stoichiometric binding of the multimeric complex. The expression of Gata2, which acts earlier in erythropoiesis [41], did not change during infection and did not differ between strains (not shown).

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