Immunogenomic profile at baseline predicts host susceptibility to clinical malaria

Introduction: Host gene and protein expression impact susceptibility to clinical malaria, but the balance of immune cell populations, cytokines and genes that contributes to protection, remains incompletely understood. Little is known about the determinants of host susceptibility to clinical malaria at a time when acquired immunity is developing. Methods: We analyzed peripheral blood mononuclear cells (PBMCs) collected from children who differed in susceptibility to clinical malaria, all from a small town in Mali. PBMCs were collected from children aged 4-6 years at the start, peak and end of the malaria season. We characterized the immune cell composition and cytokine secretion for a subset of 20 children per timepoint (10 children with no symptomatic malaria age-matched to 10 children with >2 symptomatic malarial illnesses), and gene expression patterns for six children (three per cohort) per timepoint. Results: We observed differences between the two groups of children in the expression of genes related to cell death and inflammation; in particular, inflammatory genes such as CXCL10 and STAT1 and apoptotic genes such as XAF1 were upregulated in susceptible children before the transmission season began. We also noted higher frequency of HLA-DR+ CD4 T cells in protected children during the peak of the malaria season and comparable levels cytokine secretion after stimulation with malaria schizonts across all three time points. Conclusion: This study highlights the importance of baseline immune signatures in determining disease outcome. Our data suggests that differences in apoptotic and inflammatory gene expression patterns can serve as predictive markers of susceptibility to clinical malaria.

Descrição

Funding Information: This project was funded in part by federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under grant number U19AI110820. Site development and the conduct of the original clinical trial were supported by contract N01AI85346 and cooperative agreement U19AI065683 from the National Institute of Allergy and Infectious Diseases, grant D43TW001589 from the Fogarty International Center, National Institutes of Health and contract W81XWH-06-1-0427 from the United States Department of Defense and the United States Agency for International Development for site development and the conduct of the trial. Acknowledgments Publisher Copyright: Copyright © 2023 Mbambo, Dwivedi, Ifeonu, Munro, Shrestha, Bromley, Hodges, Adkins, Kouriba, Diarra, Niangaly, Kone, Coulibaly, Traore, Dolo, Thera, Laurens, Doumbo, Plowe, Berry, Travassos, Lyke and Silva.

Palavras-chave

baseline immunity human parasite immunology immunoinformatic analysis malaria immunity malaria susceptibility mass cytometrý RNA sequencing QR180 Immunology QR Microbiology Immunology Parasitology General Biochemistry,Genetics and Molecular Biology SDG 3 - Good Health and Well-being

URI

http://hdl.handle.net/10362/164498

DOI

10.3389/fimmu.2023.1179314

Coleções

Home collection (IHMT)

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