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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.

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Mean haemoglobin titres in four C57BL/6 mice (green) and six CsA-treated C57BL/6 mice (magenta) after infection with T. congolense, and four uninfected C57BL/6 mice (black, broken line), shown as mean±SD.CsA induces defective T cells. Since there was no difference in anaemia after CsA treatment it is unlikely that T cells play a major role in the development of anaemia in C57BL/6 mice.
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pone-0005170-g003: Mean haemoglobin titres in four C57BL/6 mice (green) and six CsA-treated C57BL/6 mice (magenta) after infection with T. congolense, and four uninfected C57BL/6 mice (black, broken line), shown as mean±SD.CsA induces defective T cells. Since there was no difference in anaemia after CsA treatment it is unlikely that T cells play a major role in the development of anaemia in C57BL/6 mice.

Mentions: To find out whether T lymphocytes play a role in the development of anaemia, haemoglobin levels were compared between control and CsA-treated C57BL/6 mice. CsA is an immunosuppressive agent that induces defective T cells. No significant difference was observed in anaemia development between the two groups of mice (Fig. 3).


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)

Mean haemoglobin titres in four C57BL/6 mice (green) and six CsA-treated C57BL/6 mice (magenta) after infection with T. congolense, and four uninfected C57BL/6 mice (black, broken line), shown as mean±SD.CsA induces defective T cells. Since there was no difference in anaemia after CsA treatment it is unlikely that T cells play a major role in the development of anaemia in C57BL/6 mice.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0005170-g003: Mean haemoglobin titres in four C57BL/6 mice (green) and six CsA-treated C57BL/6 mice (magenta) after infection with T. congolense, and four uninfected C57BL/6 mice (black, broken line), shown as mean±SD.CsA induces defective T cells. Since there was no difference in anaemia after CsA treatment it is unlikely that T cells play a major role in the development of anaemia in C57BL/6 mice.
Mentions: To find out whether T lymphocytes play a role in the development of anaemia, haemoglobin levels were compared between control and CsA-treated C57BL/6 mice. CsA is an immunosuppressive agent that induces defective T cells. No significant difference was observed in anaemia development between the two groups of mice (Fig. 3).

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