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Updated: Jan 19, 2026
Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation
Tuan M Tran1, Rajan Guha2, Silvia Portugal3
1Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA; Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Ryan White Center for Pediatric Infectious Disease and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Insights
Acquired immunity to Plasmodium falciparum (Pf) malaria involves B cells, T helper pathways, and p53 activation. This immune signature predicts better control of malaria fever and parasitemia in children.
Area of Science:
- Immunology
- Systems Biology
- Infectious Diseases
Background:
- Immunity to Plasmodium falciparum (Pf) malaria develops with repeated exposure.
- Understanding this complex immune response is crucial for vaccine and therapy development.
- Limited knowledge hinders effective interventions against malaria.
Purpose of the Study:
- To investigate the immune signatures associated with differential control of parasitemia and fever in children with Pf malaria.
- To integrate multi-omics data for a comprehensive understanding of host-pathogen interactions.
- To identify host molecules influencing clinical outcomes in malaria.
Main Methods:
- Prospective systems biology study design.
- Integration of whole-blood transcriptomics, flow cytometry, and plasma cytokine/antibody profiling.
- Analysis of immune responses in children with varying abilities to control Pf infection.
Main Results:
- A pre-infection immune signature characterized by B cell enrichment, upregulated T helper type 1 (Th1) and Th2 pathways (including interferon responses), and p53 activation was linked to fever control.
- Pf-specific immunoglobulin G (IgG) and Fc receptor activation were coordinated with this signature to control parasitemia.
- Enhanced p53 expression in monocytes attenuated Plasmodium-induced inflammation and predicted fever protection.
Conclusions:
- The study identified key host immune factors contributing to differential clinical outcomes in Pf malaria.
- A specific immune profile, including p53 activation, is associated with protection against malarial fever and parasitemia.
- These findings provide a basis for developing novel vaccines and adjunctive therapies for malaria.
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.
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