Impact of Plasmodium falciparum small-sized extracellular vesicles on host peripheral blood mononuclear cells

Background: Exagerated immune activation has a key role in the pathogenesis of malaria. During blood-stage infection, Plasmodium falciparum can interact directly with host cells through infected red blood (PfiRBCs), or indirectly by release extracellular vesicles (EVs). Here, we compared impact PfiRBCs and P. small-sized EVs (PfsEVs, also known as exosomes) from Kenyan clinical isolate (PfKE12) adapted to short-term laboratory culture conditions on peripheral mononuclear (PBMC). Methods: PfsEVs were isolated cell-free culture-conditioned media ultracentrifugation while mature trophozoite purified magnetic column separation. The PfsEVs co-cultured for 18 hours PBMC. Cellular responses quantified cell surface expression markers (CD25, CD69) cytokine/chemokine levels supernatant. Results: Relative negative control conditions, induced CD25 CD4+, CD19+ CD14+ cells, CD14+ cells. Both CD69 CD8+ In addition, higher CD4+ and was significantly than that PfsEVs. Secretion MIP1α, MIP1β, GM-CSF, IL-6, IL-8, TNFα both whereas MCP-1, IL-10, IL-17α preferentially IP-10 IFN-γ PfiRBCs. Prior exposure malaria (judged antibodies schizont extract) associated lower monocyte PfsEVs. Conclusions: PfsEVs showed differential abilities induce secretion IFN-γ, suggesting former are better at inducing Th17, whilst latter Th1 respectively. reduces ability activate monocytes, tolerance may play naturally acquired anti-disease immunity.