Print Email Facebook Twitter Systems analysis and controlled malaria infection in Europeans and Africans elucidate naturally acquired immunity Title Systems analysis and controlled malaria infection in Europeans and Africans elucidate naturally acquired immunity Author de Jong, Sanne E. (Leiden University Medical Center) van Unen, Vincent (Leiden University Medical Center; Stanford University) Manurung, Mikhael D. (Leiden University Medical Center) Jochems, Simon P. (Leiden University Medical Center) Höllt, T. (TU Delft Computer Graphics and Visualisation; Leiden Computational Biology Center; Leiden University Medical Center) Pezzotti, N. (TU Delft Computer Graphics and Visualisation) Eisemann, E. (TU Delft Computer Graphics and Visualisation) Lelieveldt, B.P.F. (TU Delft Pattern Recognition and Bioinformatics; Leiden University Medical Center) Reinders, M.J.T. (TU Delft Pattern Recognition and Bioinformatics; Leiden University Medical Center; Delft Bioinformatics Lab) Date 2021 Abstract 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. To reference this document use: http://resolver.tudelft.nl/uuid:55c96f13-c660-4777-a0fe-cd591602e905 DOI https://doi.org/10.1038/s41590-021-00911-7 ISSN 1529-2908 Source Nature Immunology, 22 (5), 654-665 Part of collection Institutional Repository Document type journal article Rights © 2021 Sanne E. de Jong, Vincent van Unen, Mikhael D. Manurung, Simon P. Jochems, T. Höllt, N. Pezzotti, E. Eisemann, B.P.F. Lelieveldt, M.J.T. Reinders, More Authors Files PDF s41590_021_00911_7_1.pdf 15.97 MB Close viewer /islandora/object/uuid:55c96f13-c660-4777-a0fe-cd591602e905/datastream/OBJ/view