The online version of this article (doi:10.1186/1475-2875-11-173) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
TP designed the study, collected vivax parasites from patients, performed experiment and statistical analysis, and wrote the manuscript. WP isolated human CD34+ cells and cultured cells. PP collected human cord blood from normal full-term deliveries. CW performed analysis of cell markers and cytokine assay. SH and RU contributed substantially to the design of the study and critically revised the manuscript. All authors read and approved the final manuscript.
Severe anaemia due to dyserythropoiesis has been documented in patients infected with Plasmodium vivax, however the mechanism responsible for anaemia in vivax malaria is poorly understood. In order to better understand the role of P. vivax infection in anaemia the inhibition of erythropoiesis using haematopoietic stem cells was investigated.
Haematopoietic stem cells/CD34+ cells, isolated from normal human cord blood were used to generate growing erythroid cells. Exposure of CD34+ cells and growing erythroid cells to P. vivax parasites either from intact or lysed infected erythrocytes (IE) was examined for the effect on inhibition of cell development compared with untreated controls.
Both lysed and intact infected erythrocytes significantly inhibited erythroid growth. The reduction of erythroid growth did not differ significantly between exposure to intact and lysed IE and the mean growth relative to unexposed controls was 59.4 ± 5.2 for lysed IE and 57 ± 8.5% for intact IE. Interestingly, CD34+ cells/erythroid progenitor cells were susceptible to the inhibitory effect of P. vivax on cell expansion. Exposure to P. vivax also inhibited erythroid development, as determined by the reduced expression of glycophorin A (28.1%) and CD 71 (43.9%). Moreover, vivax parasites perturbed the division of erythroid cells, as measured by the Cytokinesis Block Proliferation Index, which was reduced to 1.35 ± 0.05 (P-value < 0.01) from a value of 2.08 ± 0.07 in controls. Neither TNF-a nor IFN-g was detected in the culture medium of erythroid cells treated with P. vivax, indicating that impaired erythropoiesis was independent of these cytokines.
This study shows for the first time that P. vivax parasites inhibit erythroid development leading to ineffective erythropoiesis and highlights the potential of P. vivax to cause severe anaemia.
Additional file 1: Erythroid cell development. Giemsa staining of cells from one to 11 day-old cultures showing CD34+ cells on day 1, and morphological characteristic of erythroid cells with haemoglobin and chromatin condensation for an orthochromic normoblasts (arrow) on day 11. Magnification X 1,000. (PDF 34 KB)12936_2012_2118_MOESM1_ESM.pdf
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