Nat Immunol

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

Sanne E. de Jong, Vincent van Unen, Mikhael D. Manurung , Koen 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 Reinders, Rolf Fendel, Stephen L. Hoffman, Peter G. Kremsner, Frits Koning, Benjamin Mordmüller, Bertrand Lell, and Maria Yazdanbakhsh

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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.

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@article{bib:de jong:2021,
    author       = { de Jong, Sanne E. and van Unen, Vincent and Manurung , Mikhael D. and Stam, Koen and Goeman, Jelle J. and Jochems, Simon P. and Höllt, Thomas and Pezzotti, Nicola and Mouwenda , Yoanne D. and Ongwe, Madeleine Eunice Betouke and Lorenz, Freia-Raphaella  and Kruize, Yvonne C. M. and Azimi, Shohreh and König, Marion and Vilanova, Anna and Eisemann, Elmar and Lelieveldt, Boudewijn P. F. and Roestenberg, Meta and Kim Lee Sim, B. and Reinders, Marcel and Fendel, Rolf and Hoffman, Stephen L. and Kremsner, Peter G. and Koning, Frits and Mordmüller, Benjamin and Lell, Bertrand and Yazdanbakhsh, Maria },    
    title        = { Systems analysis and controlled malaria infection in Europeans and Africans elucidate naturally acquired immunity },
    journal      = { Nat Immunol },
    volume       = { 22 },
    year         = { 2021 },
    pages        = { 654--665 },
    doi          = { 10.1038/s41590-021-00911-7 },
    pubmedid     = { 33888898 },
    url          = { https://publications.graphics.tudelft.nl/papers/340 },
}