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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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Expression of Snca in (A) liver and (B) spleen.Snca is strongly associated with reticulocytes and was the gene with largest expression difference that correlated with anaemia response. The strong expression of Snca in the spleen of A/J and BALB/c is suggestive of extra medullary haematopoiesis in this organ in these strains.
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pone-0005170-g008: Expression of Snca in (A) liver and (B) spleen.Snca is strongly associated with reticulocytes and was the gene with largest expression difference that correlated with anaemia response. The strong expression of Snca in the spleen of A/J and BALB/c is suggestive of extra medullary haematopoiesis in this organ in these strains.

Mentions: The function of synuclein-alpha (Snca) in erythropoiesis is not known, however an analysis of its expression in 71 tissues and cell types showed that it is expressed at maximum levels in early erythroid CD71 cells (reticulocytes) and in a separate analysis of human reticulocytes Snca was found in the top twenty most highly expressed genes [39], [40]. Snca was one of the genes with the greatest difference in mRNA abundance between C57BL/6 mice and the other two mouse strains, A/J and BALB/c, which had 60–250 fold higher expression of Snca than C57BL/6 mice in the spleen at all time points (Fig 8b). In the liver Snca expression levels were similar in all three strains until day 9 when the expression was about two fold higher in A/J and BALB/c mice than in C57BL/6 mice (Fig 8a). The transient increase in the liver could have been caused by circulating reticulocytes in anaemic animals, however the gross differences in expression in the spleen, even prior to infection, are suggestive of substantial differences in extramedullary haematopoiesis in the spleen.


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 Snca in (A) liver and (B) spleen.Snca is strongly associated with reticulocytes and was the gene with largest expression difference that correlated with anaemia response. The strong expression of Snca in the spleen of A/J and BALB/c is suggestive of extra medullary haematopoiesis in this organ in these strains.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0005170-g008: Expression of Snca in (A) liver and (B) spleen.Snca is strongly associated with reticulocytes and was the gene with largest expression difference that correlated with anaemia response. The strong expression of Snca in the spleen of A/J and BALB/c is suggestive of extra medullary haematopoiesis in this organ in these strains.
Mentions: The function of synuclein-alpha (Snca) in erythropoiesis is not known, however an analysis of its expression in 71 tissues and cell types showed that it is expressed at maximum levels in early erythroid CD71 cells (reticulocytes) and in a separate analysis of human reticulocytes Snca was found in the top twenty most highly expressed genes [39], [40]. Snca was one of the genes with the greatest difference in mRNA abundance between C57BL/6 mice and the other two mouse strains, A/J and BALB/c, which had 60–250 fold higher expression of Snca than C57BL/6 mice in the spleen at all time points (Fig 8b). In the liver Snca expression levels were similar in all three strains until day 9 when the expression was about two fold higher in A/J and BALB/c mice than in C57BL/6 mice (Fig 8a). The transient increase in the liver could have been caused by circulating reticulocytes in anaemic animals, however the gross differences in expression in the spleen, even prior to infection, are suggestive of substantial differences in extramedullary haematopoiesis in the spleen.

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