TY - JOUR
T1 - Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria
AU - Dieng, Mame Massar
AU - Diawara, Aïssatou
AU - Manikandan, Vinu
AU - Tamim El Jarkass, Hala
AU - Sermé, Samuel Sindié
AU - Sombié, Salif
AU - Barry, Aïssata
AU - Coulibaly, Sam Aboubacar
AU - Diarra, Amidou
AU - Drou, Nizar
AU - Arnoux, Marc
AU - Yousif, Ayman
AU - Tiono, Alfred B.
AU - Sirima, Sodiomon B.
AU - Soulama, Issiaka
AU - Idaghdhour, Youssef
N1 - Funding Information:
We would like to thank the children who participated in the study and their families. We thank all the individuals who facilitated sample collection and clinical work in particular Guigma Telesphore, Ouattara Aristide and the staff of the Centre National de Recherche et de Formation sur le Paludisme. We thank Wael Abdrabou for assisting with figures and various aspects of the malaria research program. We thank Kurt Warren, Ibrahim Al Hawai, Reza Rowshan, Kris Gunsalus, the NYUAD Core Bioinformatics and Technology Platform teams, Mehar Sultana and Raneem Eteer for assistance with logistics and experiments. We thank Greg Gibson and Jane Carlton for helpful discussions and suggestions. This work is supported by NYUAD Grant AD105 to Youssef Idaghdour.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-020-18915-6
DO - 10.1038/s41467-020-18915-6
M3 - Article
C2 - 33037226
AN - SCOPUS:85092502974
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 5093
ER -