A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation.
Immunity
; 51(4): 750-765.e10, 2019 10 15.
Article
in En
| MEDLINE
| ID: mdl-31492649
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Plasmodium falciparum
/
Blood Proteins
/
B-Lymphocytes
/
Tumor Suppressor Protein p53
/
Malaria, Falciparum
/
Th2 Cells
/
Th1 Cells
/
Inflammation
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Animals
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2019
Document type:
Article