Abstract
Immunity that controls parasitemia and inflammation during Plasmodium falciparum (Pf) malaria can be acquired with repeated infections. A limited understanding of this complex immune response impedes the development of vaccines and adjunctive therapies. We conducted a prospective systems biology study of children who differed in their ability to control parasitemia and fever following Pf infection. By integrating whole-blood transcriptomics, flow-cytometric analysis, and plasma cytokine and antibody profiles, we demonstrate that a pre-infection signature of B cell enrichment, upregulation of T helper type 1 (Th1) and Th2 cell-associated pathways, including interferon responses, and p53 activation associated with control of malarial fever and coordinated with Pf-specific immunoglobulin G (IgG) and Fc receptor activation to control parasitemia. Our hypothesis-generating approach identified host molecules that may contribute to differential clinical outcomes during Pf infection. As a proof of concept, we have shown that enhanced p53 expression in monocytes attenuated Plasmodium-induced inflammation and predicted protection from fever.
Original language | English (US) |
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Pages (from-to) | 750-765.e10 |
Journal | Immunity |
Volume | 51 |
Issue number | 4 |
DOIs | |
State | Published - Oct 15 2019 |
Bibliographical note
Publisher Copyright:© 2019
Keywords
- Plasmodium falciparum
- RNA sequencing
- RNA-seq
- antibody profiling
- flow cytometry
- malaria
- malaria immunity
- prospective cohort study
- systems biology
- systems immunology
- transcriptomics
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Research Support, N.I.H., Intramural
- Journal Article
- Research Support, N.I.H., Extramural