Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria.

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.

• Authors: Mame Massar Dieng, Aïssatou Diawara, Vinu Manikandan, Hala Tamim El Jarkass, Samuel Sindié Sermé, Salif Sombié, Aïssata Barry, Sam Aboubacar Coulibaly, Amidou Diarra, Nizar Drou, Marc Arnoux, Ayman Yousif, Alfred B Tiono, Sodiomon B Sirima, Issiaka Soulama, Youssef Idaghdour
• Journal: Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 5093 (10 09 2020) ISSN: 2041-1723 [Electronic] England
• PMID: 33037226 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN-598 microRNA, human
• MicroRNAs
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger

Topics

• Burkina Faso
• Child
• Child, Preschool
• Gene Expression Regulation
• Genome, Human
• Humans
• Immune Evasion (genetics)
• Longitudinal Studies
• Malaria, Falciparum (genetics, immunology)
• MicroRNAs (genetics)
• Parasitemia (genetics, immunology)
• Plasmodium falciparum (immunology, pathogenicity)
• Polymorphism, Single Nucleotide
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• RNA, Messenger (genetics)
• Whole Genome Sequencing