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Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria
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-tran...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547729/ https://www.ncbi.nlm.nih.gov/pubmed/33037226 http://dx.doi.org/10.1038/s41467-020-18915-6 |
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author | Dieng, Mame Massar Diawara, Aïssatou Manikandan, Vinu Tamim El Jarkass, Hala Sermé, Samuel Sindié Sombié, Salif Barry, Aïssata Coulibaly, Sam Aboubacar Diarra, Amidou Drou, Nizar Arnoux, Marc Yousif, Ayman Tiono, Alfred B. Sirima, Sodiomon B. Soulama, Issiaka Idaghdour, Youssef |
author_facet | Dieng, Mame Massar Diawara, Aïssatou Manikandan, Vinu Tamim El Jarkass, Hala Sermé, Samuel Sindié Sombié, Salif Barry, Aïssata Coulibaly, Sam Aboubacar Diarra, Amidou Drou, Nizar Arnoux, Marc Yousif, Ayman Tiono, Alfred B. Sirima, Sodiomon B. Soulama, Issiaka Idaghdour, Youssef |
author_sort | Dieng, Mame Massar |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7547729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75477292020-10-19 Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria Dieng, Mame Massar Diawara, Aïssatou Manikandan, Vinu Tamim El Jarkass, Hala Sermé, Samuel Sindié Sombié, Salif Barry, Aïssata Coulibaly, Sam Aboubacar Diarra, Amidou Drou, Nizar Arnoux, Marc Yousif, Ayman Tiono, Alfred B. Sirima, Sodiomon B. Soulama, Issiaka Idaghdour, Youssef Nat Commun Article 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. Nature Publishing Group UK 2020-10-09 /pmc/articles/PMC7547729/ /pubmed/33037226 http://dx.doi.org/10.1038/s41467-020-18915-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Dieng, Mame Massar Diawara, Aïssatou Manikandan, Vinu Tamim El Jarkass, Hala Sermé, Samuel Sindié Sombié, Salif Barry, Aïssata Coulibaly, Sam Aboubacar Diarra, Amidou Drou, Nizar Arnoux, Marc Yousif, Ayman Tiono, Alfred B. Sirima, Sodiomon B. Soulama, Issiaka Idaghdour, Youssef Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria |
title | Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria |
title_full | Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria |
title_fullStr | Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria |
title_full_unstemmed | Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria |
title_short | Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria |
title_sort | integrative genomic analysis reveals mechanisms of immune evasion in p. falciparum malaria |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547729/ https://www.ncbi.nlm.nih.gov/pubmed/33037226 http://dx.doi.org/10.1038/s41467-020-18915-6 |
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