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

Abstract

BackgroundTo 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.MethodsA 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.ResultsIn 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.ConclusionThese 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1781-4) contains supplementary material, which is available to authorized users.

An Overview of Peripheral Blood Mononuclear Cells as a Model for Immunological Research of Toxoplasma gondii and Other Apicomplexan Parasites

“…The donors' immunological histories could influence this strong heterogeneous response because these PBMCs could present cross-reactivity with other infections such as schistosomiasis, leishmaniosis, toxoplasmosis, and Chagas disease. For this reason, other authors have proposed alternatives to the use of PBMCs in studying the primary immune response; one such alternative are hematopoietic stem cells (naïve cells), which would reduce the discrepancies in mononuclear cell quality between studies (Chitsanoor et al, 2017).…”

“…The evidence suggests that PBMCs could be a good model for studying the immune response in apicomplexan parasites and for evaluating the efficiency of vaccine candidates, therapeutic agents and immunomodulatory molecules. However, these cells are not the most appropriate model for studying primo-infections (Chitsanoor et al, 2017). Therefore, despite all the benefits of the PBMC model, precautions should be taken related to its limitations and the type of immune response that is being evaluated.…”

The Rough Guide to Monocytes in Malaria Infection

“…Exposure to P. falciparum iRBCs also alters monocyte activation. It resulted in upregulation of HLA-DR expression on naïve monocytes derived from haematopoietic stem cells (32). Monocytes from PBMCs of Papua New Guinean children with severe malaria responded in vitro to P. falciparum iRBCs by secreting higher quantities of TNF-α, MIP-1β, and MIP-1α (implicated in monocyte activation and recruitment) than healthy children or children with uncomplicated malaria (33).…”

“…This is consistent with training or tolerance effects that could explain the contradictory behavior of monocytes observed across different settings, independent of differences in protocols and analysis. To minimize these discrepancies, Udomsangpetch et al have developed a model of mononuclear cells generated from hematopoietic stem cells, that evaluates in vitro the interaction between naïve immune cells and malaria parasites (32). Whole genome association studies (GWAS) might be used as a tool to identify genetic differences that can further explain why monocytes respond differently across geographical areas (103, 104).…”