Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria.
Burkina Faso
Child
Child, Preschool
Gene Expression Regulation
Genome, Human
Humans
Immune Evasion
/ genetics
Longitudinal Studies
Malaria, Falciparum
/ genetics
MicroRNAs
/ genetics
Parasitemia
/ genetics
Plasmodium falciparum
/ immunology
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins c-bcl-2
/ genetics
RNA, Messenger
/ genetics
Whole Genome Sequencing
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 10 2020
09 10 2020
Historique:
received:
24
01
2020
accepted:
16
09
2020
entrez:
10
10
2020
pubmed:
11
10
2020
medline:
3
11
2020
Statut:
epublish
Résumé
The mechanisms behind the ability of Plasmodium falciparum to evade host immune system are poorly understood and are a major roadblock in achieving malaria elimination. Here, we use integrative genomic profiling and a longitudinal pediatric cohort in Burkina Faso to demonstrate the role of post-transcriptional regulation in host immune response in malaria. We report a strong signature of miRNA expression differentiation associated with P. falciparum infection (127 out of 320 miRNAs, B-H FDR 5%) and parasitemia (72 miRNAs, B-H FDR 5%). Integrative miRNA-mRNA analysis implicates several infection-responsive miRNAs (e.g., miR-16-5p, miR-15a-5p and miR-181c-5p) promoting lymphocyte cell death. miRNA cis-eQTL analysis using whole-genome sequencing data identified 1,376 genetic variants associated with the expression of 34 miRNAs (B-H FDR 5%). We report a protective effect of rs114136945 minor allele on parasitemia mediated through miR-598-3p expression. These results highlight the impact of post-transcriptional regulation, immune cell death processes and host genetic regulatory control in malaria.
Identifiants
pubmed: 33037226
doi: 10.1038/s41467-020-18915-6
pii: 10.1038/s41467-020-18915-6
pmc: PMC7547729
doi:
Substances chimiques
MIRN-598 microRNA, human
0
MicroRNAs
0
Proto-Oncogene Proteins c-bcl-2
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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