| Literature DB >> 33888898 |
Vincent van Unen1,2,3, Mikhael D Manurung1, Koen A Stam1, Sanne E de Jong1, Jelle J Goeman4, Simon P Jochems1, Thomas Höllt5,6, Nicola Pezzotti5, Yoanne D Mouwenda1,7, Madeleine Eunice Betouke Ongwe1,7,8, Freia-Raphaella Lorenz9,10, Yvonne C M Kruize1, Shohreh Azimi1, Marion H König1, Anna Vilanova5, Elmar Eisemann5, Boudewijn P F Lelieveldt5,11, Meta Roestenberg1, B Kim Lee Sim12, Marcel J T Reinders4,13, Rolf Fendel9,10, Stephen L Hoffman12, Peter G Kremsner7,9,10, Frits Koning2, Benjamin Mordmüller7,9,10,14, Bertrand Lell7,15, Maria Yazdanbakhsh16.
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.Entities:
Year: 2021 PMID： 33888898 DOI： 10.1038/s41590-021-00911-7
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606