A novel in vitro model reveals distinctive modulatory roles of Plasmodium falciparum and Plasmodium vivax on naïve cell-mediated immunity

一种新型体外模型揭示了恶性疟原虫和间日疟原虫对幼稚细胞介导免疫的独特调节作用

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作者:Setthakit Chitsanoor, Sangdao Somsri, Panyu Panburana, Mathirut Mungthin, Ratawan Ubalee, Maliwan Emyeam, Somchai Jongwutiwes, Jetsumon Sattabongkot, Rachanee Udomsangpetch

Background

To date, human peripheral blood mononuclear cells (PBMCs) have been used mainly in immune stimulation assays and the interpretation of data can be influenced by the previous immunological history of donors and cross reactivity with other infectious agents. Resolving these limitations requires an alternative in vitro model to uncover the primary response profiles.

Conclusion

These results suggest that naïve mononuclear cells differentiated in vitro from HSCs could provide a valid model for the assessment of immunity. P. falciparum and P. vivax malaria parasites could modulate various populations of immune cells starting from newly differentiated mononuclear cells.

Methods

A novel in vitro model of mononuclear cells (MNCs) generated from haematopoietic stem cells (HSCs) was developed and these cells were then co-cultured with various antigens from Plasmodium falciparum and Plasmodium vivax to investigate the response of naïve immune cells to malaria antigens by flow cytometry.

Results

In vitro stimulation of naïve lymphocytes showed that CD4+ and CD8+ T lymphocytes were significantly reduced (P < 0.01) by exposure to lysates of infected erythrocytes or intact erythrocytes infected with P. falciparum. The depletion was associated with the expression of CD95 (Fas receptor) on the surface of T lymphocytes. Maturation of T lymphocytes was affected differently, showing elevated CD3+CD4+CD8+ and CD3+CD4-CD8- T lymphocytes after stimulation with cell lysates of P. falciparum and P. vivax, respectively. In addition, antigen presenting monocytes and dendritic cells derived from haematopoietic stem cells showed impaired HLA-DR expression as a consequence of exposure to different species of malaria parasites.

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