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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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Erythrocyte structural proteins.Expression of erythrocyte structural protein genes followed the expression of their transcription factors (Fig 8) and C57BL/6 had lower expression levels than A/J or BALB/c.
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pone-0005170-g010: Erythrocyte structural proteins.Expression of erythrocyte structural protein genes followed the expression of their transcription factors (Fig 8) and C57BL/6 had lower expression levels than A/J or BALB/c.

Mentions: Spectrin alpha and beta (Spna1 and Spnb1), Glycophorin (Gypa) and erythrocyte protein band 7 Epb7.2 all declined in production in the spleen post infection but recovered by day 17 (Fig 10). In each case C57BL/6 had the lowest level of transcription consistent with relatively low levels of haematopoiesis. The expression of these genes tightly followed that of the regulatory genes described above (Fig 9) in both expression levels and in the decline from day zero to day seven followed by the recovery of expression to day 17. Haemoglobin-alpha (Hba-a1) was the most highly expressed gene in the spleen from day 0 and its expression changed little over the course of the infection but was 2–4 fold higher in BALB/c than A/J or C57BL/6 in both liver and spleen respectively (Fig 10). Haemoglobin beta expression was invariant and similar amongst all 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)

Erythrocyte structural proteins.Expression of erythrocyte structural protein genes followed the expression of their transcription factors (Fig 8) and C57BL/6 had lower expression levels than A/J or BALB/c.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0005170-g010: Erythrocyte structural proteins.Expression of erythrocyte structural protein genes followed the expression of their transcription factors (Fig 8) and C57BL/6 had lower expression levels than A/J or BALB/c.
Mentions: Spectrin alpha and beta (Spna1 and Spnb1), Glycophorin (Gypa) and erythrocyte protein band 7 Epb7.2 all declined in production in the spleen post infection but recovered by day 17 (Fig 10). In each case C57BL/6 had the lowest level of transcription consistent with relatively low levels of haematopoiesis. The expression of these genes tightly followed that of the regulatory genes described above (Fig 9) in both expression levels and in the decline from day zero to day seven followed by the recovery of expression to day 17. Haemoglobin-alpha (Hba-a1) was the most highly expressed gene in the spleen from day 0 and its expression changed little over the course of the infection but was 2–4 fold higher in BALB/c than A/J or C57BL/6 in both liver and spleen respectively (Fig 10). Haemoglobin beta expression was invariant and similar amongst all 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