Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

<ns4:p><ns4:bold>Background: </ns4:bold>Exagerated immune activation has a key role in the pathogenesis of malaria<ns4:bold>. </ns4:bold>During blood-stage infection, <ns4:italic>Plasmodium falciparum</ns4:italic> can interact directly with host immune cells through infected red blood cells (<ns4:italic>Pf</ns4:italic>iRBCs), or indirectly by the release of extracellular vesicles (EVs). Here, we compared the impact of <ns4:italic>Pf</ns4:italic>iRBCs and <ns4:italic>P. falciparum</ns4:italic> small-sized EVs (<ns4:italic>Pf</ns4:italic>sEVs, also known as exosomes) from a Kenyan clinical isolate (<ns4:italic>Pf</ns4:italic>KE12) adapted to short-term laboratory culture conditions on host peripheral blood mononuclear cells (PBMC).</ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold><ns4:italic> Pf</ns4:italic>sEVs were isolated from cell-free culture-conditioned media by ultracentrifugation while mature trophozoite <ns4:italic>Pf</ns4:italic>iRBCs were purified by magnetic column separation. The <ns4:italic>Pf</ns4:italic>sEVs and the <ns4:italic>Pf</ns4:italic>iRBCs were co-cultured for 18 hours with PBMC. Cellular responses were quantified by cell surface expression of activation markers (CD25, CD69) and cytokine/chemokine levels in the supernatant.</ns4:p><ns4:p> <ns4:bold>Results:</ns4:bold> Relative to negative control conditions,<ns4:italic> Pf</ns4:italic>sEVs induced CD25 expression on CD4<ns4:sup>+</ns4:sup>, CD19<ns4:sup>+</ns4:sup> and CD14<ns4:sup>+ </ns4:sup>cells, while <ns4:italic>Pf</ns4:italic>iRBCs induced on CD19<ns4:sup>+</ns4:sup> and CD14<ns4:sup>+</ns4:sup> cells. Both <ns4:italic>Pf</ns4:italic>sEVs and <ns4:italic>Pf</ns4:italic>iRBCs induced CD69 on CD4<ns4:sup>+</ns4:sup>, CD8<ns4:sup>+</ns4:sup> and CD19<ns4:sup>+</ns4:sup> cells. In addition, <ns4:italic>Pf</ns4:italic>iRBCs induced higher expression of CD69 on CD14<ns4:sup>+</ns4:sup> cells. CD69 induced by <ns4:italic>Pf</ns4:italic>iRBCs on CD4<ns4:sup>+ </ns4:sup>and CD19<ns4:sup>+</ns4:sup> cells was significantly higher than that induced by <ns4:italic>Pf</ns4:italic>sEVs. Secretion of MIP1α, MIP1β, GM-CSF, IL-6, IL-8, and TNFα were significantly induced by both <ns4:italic>Pf</ns4:italic>sEVs and <ns4:italic>Pf</ns4:italic>iRBCs whereas MCP-1, IL-10, IL-17α  were preferentially induced by <ns4:italic>Pf</ns4:italic>sEVs and IP-10 and IFN-γ by <ns4:italic>Pf</ns4:italic>iRBCs. Prior exposure to malaria (judged by antibodies to schizont extract) was associated with lower monocyte responses to <ns4:italic>Pf</ns4:italic>sEVs.</ns4:p><ns4:p> <ns4:bold>Conclusions: </ns4:bold><ns4:italic>Pf</ns4:italic>sEVs and <ns4:italic>Pf</ns4:italic>iRBCs showed differential abilities to induce secretion of IL-17α  and IFN-γ, suggesting that the former are better at inducing Th17, whilst  the latter induce Th1 immune responses respectively. Prior exposure to malaria significantly reduces the ability of <ns4:italic>Pf</ns4:italic>sEVs to activate monocytes, suggesting immune tolerance to <ns4:italic>Pf</ns4:italic>sEVs may play a role in naturally acquired  anti-disease immunity.</ns4:p>

Original publication




Journal article


Wellcome Open Research


F1000 Research Ltd

Publication Date





197 - 197