Limits...
The protozoan parasite Theileria annulata alters the differentiation state of the infected macrophage and suppresses musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors.

Jensen K, Makins GD, Kaliszewska A, Hulme MJ, Paxton E, Glass EJ - Int. J. Parasitol. (2009)

Bottom Line: Furthermore, mRNA levels for c-maf and the closely related transcription factor mafB were significantly lower in established T. annulata-infected cell-lines than in bovine monocyte-derived m phi.We believe these results provide the first direct evidence that T. annulata modulates the host m phi differentiation state, which may diminish the defence capabilities of the infected cell and/or promote cell proliferation.Musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors play an important role in cell proliferation, differentiation and survival; therefore, regulation of these genes may be a major mechanism employed by T. annulata to survive within the infected m phi.

View Article: PubMed Central - PubMed

Affiliation: Division of Genetics & Genomics, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin Biocentre, Midlothian EH25 9PS, UK. Kirsty.Jensen@roslin.ed.ac.uk

ABSTRACT
The tick-borne protozoan parasite Theileria annulata causes a debilitating disease of cattle called Tropical Theileriosis. The parasite predominantly invades bovine macrophages (m phi) and induces host cell transformation by a mechanism that has not been fully elucidated. Infection is associated with loss of characteristic m phi functions and phenotypic markers, indicative of host cell de-differentiation. We have investigated the effect of T. annulata infection on the expression of the m phi differentiation marker c-maf. The up-regulation of c-maf mRNA levels observed during bovine monocyte differentiation to m phi was suppressed by T. annulata infection. Furthermore, mRNA levels for c-maf and the closely related transcription factor mafB were significantly lower in established T. annulata-infected cell-lines than in bovine monocyte-derived m phi. Treatment of T. annulata-infected cells with the theileriacidal drug buparvaquone induced up-regulation of c-maf and mafB, which correlated with altered expression of down-stream target genes, e.g. up-regulation of integrin B7 and down-regulation of IL12A. Furthermore, T. annulata infection is associated with the suppression of the transcription factors, Pu.1 and RUNX1, and colony stimulating factor 1 receptor (CSF1R) which are also involved in the regulation of monocyte/m phi differentiation. We believe these results provide the first direct evidence that T. annulata modulates the host m phi differentiation state, which may diminish the defence capabilities of the infected cell and/or promote cell proliferation. Musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors play an important role in cell proliferation, differentiation and survival; therefore, regulation of these genes may be a major mechanism employed by T. annulata to survive within the infected m phi.

Show MeSH

Related in: MedlinePlus

The expression of musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors MAFB and c-MAF is suppressed in Theileria annulata-infected cell-lines. Average log2 c-MAF (grey bars) and MAFB (white bars) mRNA fold difference in bovine monocytes, bovine monocyte-derived macrophages (mϕ) and T. annulata-infected cell-lines compared with a standard resting monocyte sample. The error bars indicate the standard error for eight biological replicates for monocytes and bovine monocyte-derived mϕ and 10 ex vivo derived T. annulata-infected cell-lines. The statistical significance of the difference in mRNA levels between the T. annulata-infected cells and uninfected monocytes or bovine monocyte-derived mϕ is indicated and ** denotes P ⩽ 0.001.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2723921&req=5

fig3: The expression of musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors MAFB and c-MAF is suppressed in Theileria annulata-infected cell-lines. Average log2 c-MAF (grey bars) and MAFB (white bars) mRNA fold difference in bovine monocytes, bovine monocyte-derived macrophages (mϕ) and T. annulata-infected cell-lines compared with a standard resting monocyte sample. The error bars indicate the standard error for eight biological replicates for monocytes and bovine monocyte-derived mϕ and 10 ex vivo derived T. annulata-infected cell-lines. The statistical significance of the difference in mRNA levels between the T. annulata-infected cells and uninfected monocytes or bovine monocyte-derived mϕ is indicated and ** denotes P ⩽ 0.001.

Mentions: The expression of c-MAF and MAFB in 10 ex vivo-derived T. annulata-infected cell-lines was compared with that measured in resting monocytes and mϕ by qRT-PCR (Fig. 3). Levels of c-MAF mRNA in the T. annulata-infected cell-lines were not statistically different from those measured in resting monocytes. However, there was a statistically significant difference in c-MAF levels measured in differentiated mϕ and T. annulata-infected cell-lines (P < 0.001). In addition, MAFB mRNA levels were statistically significantly lower (P < 0.001) in T. annulata-infected cell-lines than in resting monocytes and mature mϕ, exhibiting on average a 9900-fold decrease in expression. The T. annulata-infected cell-lines are believed to be of mϕ origin and, therefore, these results provide evidence that transcription of both c-MAF and MAFB is suppressed by T. annulata infection.


The protozoan parasite Theileria annulata alters the differentiation state of the infected macrophage and suppresses musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors.

Jensen K, Makins GD, Kaliszewska A, Hulme MJ, Paxton E, Glass EJ - Int. J. Parasitol. (2009)

The expression of musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors MAFB and c-MAF is suppressed in Theileria annulata-infected cell-lines. Average log2 c-MAF (grey bars) and MAFB (white bars) mRNA fold difference in bovine monocytes, bovine monocyte-derived macrophages (mϕ) and T. annulata-infected cell-lines compared with a standard resting monocyte sample. The error bars indicate the standard error for eight biological replicates for monocytes and bovine monocyte-derived mϕ and 10 ex vivo derived T. annulata-infected cell-lines. The statistical significance of the difference in mRNA levels between the T. annulata-infected cells and uninfected monocytes or bovine monocyte-derived mϕ is indicated and ** denotes P ⩽ 0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2723921&req=5

fig3: The expression of musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors MAFB and c-MAF is suppressed in Theileria annulata-infected cell-lines. Average log2 c-MAF (grey bars) and MAFB (white bars) mRNA fold difference in bovine monocytes, bovine monocyte-derived macrophages (mϕ) and T. annulata-infected cell-lines compared with a standard resting monocyte sample. The error bars indicate the standard error for eight biological replicates for monocytes and bovine monocyte-derived mϕ and 10 ex vivo derived T. annulata-infected cell-lines. The statistical significance of the difference in mRNA levels between the T. annulata-infected cells and uninfected monocytes or bovine monocyte-derived mϕ is indicated and ** denotes P ⩽ 0.001.
Mentions: The expression of c-MAF and MAFB in 10 ex vivo-derived T. annulata-infected cell-lines was compared with that measured in resting monocytes and mϕ by qRT-PCR (Fig. 3). Levels of c-MAF mRNA in the T. annulata-infected cell-lines were not statistically different from those measured in resting monocytes. However, there was a statistically significant difference in c-MAF levels measured in differentiated mϕ and T. annulata-infected cell-lines (P < 0.001). In addition, MAFB mRNA levels were statistically significantly lower (P < 0.001) in T. annulata-infected cell-lines than in resting monocytes and mature mϕ, exhibiting on average a 9900-fold decrease in expression. The T. annulata-infected cell-lines are believed to be of mϕ origin and, therefore, these results provide evidence that transcription of both c-MAF and MAFB is suppressed by T. annulata infection.

Bottom Line: Furthermore, mRNA levels for c-maf and the closely related transcription factor mafB were significantly lower in established T. annulata-infected cell-lines than in bovine monocyte-derived m phi.We believe these results provide the first direct evidence that T. annulata modulates the host m phi differentiation state, which may diminish the defence capabilities of the infected cell and/or promote cell proliferation.Musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors play an important role in cell proliferation, differentiation and survival; therefore, regulation of these genes may be a major mechanism employed by T. annulata to survive within the infected m phi.

View Article: PubMed Central - PubMed

Affiliation: Division of Genetics & Genomics, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin Biocentre, Midlothian EH25 9PS, UK. Kirsty.Jensen@roslin.ed.ac.uk

ABSTRACT
The tick-borne protozoan parasite Theileria annulata causes a debilitating disease of cattle called Tropical Theileriosis. The parasite predominantly invades bovine macrophages (m phi) and induces host cell transformation by a mechanism that has not been fully elucidated. Infection is associated with loss of characteristic m phi functions and phenotypic markers, indicative of host cell de-differentiation. We have investigated the effect of T. annulata infection on the expression of the m phi differentiation marker c-maf. The up-regulation of c-maf mRNA levels observed during bovine monocyte differentiation to m phi was suppressed by T. annulata infection. Furthermore, mRNA levels for c-maf and the closely related transcription factor mafB were significantly lower in established T. annulata-infected cell-lines than in bovine monocyte-derived m phi. Treatment of T. annulata-infected cells with the theileriacidal drug buparvaquone induced up-regulation of c-maf and mafB, which correlated with altered expression of down-stream target genes, e.g. up-regulation of integrin B7 and down-regulation of IL12A. Furthermore, T. annulata infection is associated with the suppression of the transcription factors, Pu.1 and RUNX1, and colony stimulating factor 1 receptor (CSF1R) which are also involved in the regulation of monocyte/m phi differentiation. We believe these results provide the first direct evidence that T. annulata modulates the host m phi differentiation state, which may diminish the defence capabilities of the infected cell and/or promote cell proliferation. Musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors play an important role in cell proliferation, differentiation and survival; therefore, regulation of these genes may be a major mechanism employed by T. annulata to survive within the infected m phi.

Show MeSH
Related in: MedlinePlus