title: A novel in vitro model reveals distinctive modulatory roles of Plasmodium falciparum and Plasmodium vivax on naïve cell-mediated immunity.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Setthakit
authors.initials: S
authors.lastname: Chitsanoor
authors.affiliation: Graduate Programme in Biomedical Science, Faculty of Allied Health Sciences, Thammasart University, Pathumthani, Thailand.
authors.forename: Sangdao
authors.initials: S
authors.lastname: Somsri
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine Ramathibodhi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Panyu
authors.initials: P
authors.lastname: Panburana
authors.affiliation: Department of Parasitology, Phramongkutklao College of Medicine, Bangkok, 10400, Thailand.
authors.forename: Mathirut
authors.initials: M
authors.lastname: Mungthin
authors.affiliation: Department of Entomology, USAMC Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Ratawan
authors.initials: R
authors.lastname: Ubalee
authors.affiliation: Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Maliwan
authors.initials: M
authors.lastname: Emyeam
authors.affiliation: Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Somchai
authors.initials: S
authors.lastname: Jongwutiwes
authors.affiliation: Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.affiliation: Centers for Emerging and Neglected Infectious Diseases, Mahidol University, Bangkok, Thailand. rachanee.udo@mahidol.ac.th.|Centers for Research and Innovation, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand. rachanee.udo@mahidol.ac.th.
authors.forename: Rachanee
authors.identifier: 0000-0003-4780-4914
authors.initials: R
authors.lastname: Udomsangpetch
mesh_terms: D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D016780:Malaria, Vivax / Q000276:immunology* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology*; D010966:Plasmodium vivax / Q000276:immunology*
keywords: Cell mediated immunity; Hematopoietic stem cells; Malaria