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Systems analysis and controlled malaria infection in Europeans and Africans elucidate naturally acquired immunity

2021; Nature Portfolio; Volume: 22; Issue: 5 Linguagem: Inglês

10.1038/s41590-021-00911-7

1529-2916

De Jong, Vincent van Unen, Mikhael D. Manurung, Koen A. Stam, Jelle J. Goeman, Simon P. Jochems, Thomas Höllt, Nicola Pezzotti, Yoanne D. Mouwenda, Madeleine Eunice Betouke Ongwe, Freia-Raphaella Lorenz, Yvonne C. M. Kruize, Shohreh Azimi, Marion König, Anna Vilanova, Elmar Eisemann, Boudewijn P. F. Lelieveldt, Meta Roestenberg, B. Kim Lee Sim, Marcel J. T. Reinders, Rolf Fendel, Stephen L. Hoffman, Peter G. Kremsner, Frits Koning, Benjamin Mordmüller, Bertrand Lell, Maria Yazdanbakhsh,

Zoonotic diseases and public health

Controlled human infections provide opportunities to study the interaction between the immune system and malaria parasites, which is essential for vaccine development. Here, we compared immune signatures of malaria-naive Europeans and of Africans with lifelong malaria exposure using mass cytometry, RNA sequencing and data integration, before and 5 and 11 days after venous inoculation with Plasmodium falciparum sporozoites. We observed differences in immune cell populations, antigen-specific responses and gene expression profiles between Europeans and Africans and among Africans with differing degrees of immunity. Before inoculation, an activated/differentiated state of both innate and adaptive cells, including elevated CD161+CD4+ T cells and interferon-γ production, predicted Africans capable of controlling parasitemia. After inoculation, the rapidity of the transcriptional response and clusters of CD4+ T cells, plasmacytoid dendritic cells and innate T cells were among the features distinguishing Africans capable of controlling parasitemia from susceptible individuals. These findings can guide the development of a vaccine effective in malaria-endemic regions. Malaria immunity can be acquired through natural infection, but the correlates of protection are still being determined. Yazdanbakhsh and colleagues combine experimental infection of volunteers with Plasmodium falciparum with systems analysis to throw light on the nature of protective immune responses.