Back to Search
Start Over
Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria.
- Source :
-
Nature communications [Nat Commun] 2020 Oct 09; Vol. 11 (1), pp. 5093. Date of Electronic Publication: 2020 Oct 09. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Burkina Faso
Child
Child, Preschool
Gene Expression Regulation
Genome, Human
Humans
Longitudinal Studies
Parasitemia genetics
Parasitemia immunology
Plasmodium falciparum immunology
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins c-bcl-2 genetics
RNA, Messenger genetics
Whole Genome Sequencing
Immune Evasion genetics
Malaria, Falciparum genetics
Malaria, Falciparum immunology
MicroRNAs genetics
Plasmodium falciparum pathogenicity
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 33037226
- Full Text :
- https://doi.org/10.1038/s41467-020-18915-6