Systems analysis and controlled malaria infection in Europeans and Africans elucidate naturally acquired immunity
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Publication year
2021Author(s)
Source
Nature Immunology, 22, 5, (2021), pp. 654-665ISSN
Publication type
Article / Letter to editor
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Organization
Medical Microbiology
Journal title
Nature Immunology
Volume
vol. 22
Issue
iss. 5
Page start
p. 654
Page end
p. 665
Subject
Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Medical Microbiology - Radboud University Medical CenterAbstract
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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