Abstract
BackgroundReduction in the number of circulating blood lymphocytes (lymphocytopaenia) has been reported during clinical episodes of malaria and is normalized after treatment with anti-malaria drugs. While this phenomenon is well established in malaria infection, the underlying mechanisms are still not fully elucidated. In the present study, the occurrence of apoptosis and its pathways in CD4+ T cells was investigated in naturally Plasmodium vivax-infected individuals from a Brazilian endemic area (Porto Velho – RO).MethodsBlood samples were collected from P. vivax-infected individuals and healthy donors. The apoptosis was characterized by cell staining with Annexin V/FITC and propidium iodide and the apoptosis-associated gene expression profile was carried out using RT2 Profiler PCR Array–Human Apoptosis. The plasma TNF level was determined by ELISA. The unpaired t-test or Mann–Whitney test was applied according to the data distribution.ResultsPlasmodium vivax-infected individuals present low number of leukocytes and lymphocytes with a higher percentage of CD4+ T cells in early and/or late apoptosis. Increased gene expression was observed for TNFRSF1B and Bid, associated with a reduction of Bcl-2, in individuals with P. vivax malaria. Furthermore, these individuals showed increased plasma levels of TNF compared to malaria-naive donors.ConclusionsThe results of the present study suggest that P. vivax infection induces apoptosis of CD4+ T cells mediated by two types of signaling: by activation of the TNFR1 death receptor (extrinsic pathway), which is amplified by Bid, and by decreased expression of the anti-apoptotic protein Bcl-2 (intrinsic pathway). The T lymphocytes apoptosis could reflect a strategy of immune evasion triggered by the parasite, enabling their persistence but also limiting the occurrence of immunopathology.Electronic supplementary materialThe online version of this article (doi:10.1186/1475-2875-14-5) contains supplementary material, which is available to authorized users.
Highlights
Reduction in the number of circulating blood lymphocytes has been reported during clinical episodes of malaria and is normalized after treatment with anti-malaria drugs
Plasmodium vivax infection leads to leukopaenia, lymphocytopaenia and other haematological alterations Previous reports have shown that malaria infection leads to alterations in haematological parameters during acute clinical episodes [5,7,8,9]
Plasmodium vivax infection induces apoptosis of CD4+ T cells To determine whether the reduction in the number of lymphocytes was due to apoptosis of CD4+ T cells, whole blood samples of both P. vivax-infected donors and malaria-naive donors were stained with Annexin-V, propidium iodide (PI) and anti-CD4 antibody (Figure 1A)
Summary
Reduction in the number of circulating blood lymphocytes (lymphocytopaenia) has been reported during clinical episodes of malaria and is normalized after treatment with anti-malaria drugs. While this phenomenon is well established in malaria infection, the underlying mechanisms are still not fully elucidated. A decrease in the number of circulating blood lymphocytes (lymphocytopaenia) is a well-documented phenomenon in naturally infected individuals during acute Plasmodium falciparum [1,2,3,4,5,6] and Plasmodium vivax [5,7,8,9]. T cells at sites of inflammation, followed by reappearance of these cells in the blood during the treatment [3,14,15].
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