Format:
26
,
Illustrationen
ISSN:
1365-2567
Content:
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.
Note:
Published: September 3, 2019
,
Gesehen am 13.11.2019
In:
Immunology, Oxford [u.a.] : Wiley-Blackwell, 1958, 51(2019), 4, Seite 750-765, e1-e10, 1365-2567
In:
volume:51
In:
year:2019
In:
number:4
In:
pages:750-765, e1-e10
In:
extent:26
Language:
English
DOI:
10.1016/j.immuni.2019.08.009
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