[en] Africa's environmental, cultural, and genetic diversity can profoundly shape population responses to infectious diseases, including malaria caused by Plasmodium falciparum. Differences in malaria susceptibility among populations are documented, but the underlying mechanisms remain poorly understood. Notably, the Fulani ethnic group in Africa is less susceptible to malaria compared to other sympatric groups, such as the Mossi. They exhibit lower disease rates and parasite load as well as enhanced serological protection. However, elucidating the molecular and cellular basis of this protection has been challenging in part due to limited immunological characterization at the cellular level. To address this question, we performed single-cell transcriptomic profiling of peripheral blood mononuclear cells from 126 infected and non-infected Fulani and Mossi children in rural Burkina Faso. This analysis generated over 70,000 single-cell transcriptomes and identified 30 distinct cell subtypes. We report a profound effect of ethnicity on the transcriptional landscape, particularly within monocyte populations. Differential expression analysis across cell subtypes revealed ethnic-specific immune signatures under both infected and non-infected states. Specifically, monocytes and T cell subtypes of the Fulani exhibited reduced pro-inflammatory responses, while their B cell subtypes displayed stronger activation and inflammatory profiles. Furthermore, single-cell expression quantitative trait locus (eQTL) analysis in monocytes of infected children revealed several significant regulatory variants with ethnicity-specific effects on immune-related genes, including CD36 and MT2A. Overall, we identify ethnic, cell-type-specific, and genetic regulatory effects on host immune responses to malaria and provide valuable single-cell eQTL and transcriptomic datasets from under-represented populations.
Disciplines :
Genetics & genetic processes
Author, co-author :
Shahin, Tala; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
Jurkovic, Jakub; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
Dieng, Mame ; Université de Liège - ULiège > TERRA Research Centre ; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
Manikandan, Vinu; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
Abdrabou, Wael; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
Alamad, Bana; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
Bayaraa, Odmaa; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
Diawara, Aïssatou; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
Sermé, Samuel Sindié; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso
Henry, Noëlie Béré; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso
Sombie, Salif; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso
Almojil, Dareen; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
Arnoux, Marc; Core Technology Platforms, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
Drou, Nizar; Center for Genomics and Systems Biology, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
Soulama, Issiaka; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso, Institut de Recherche en Sciences de la Santé (IRSS)/CNRST, 03 BP 7192, Ouagadougou, Burkina Faso
Idaghdour, Youssef ; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates, Center for Genomics and Systems Biology, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates. Electronic address: youssef.idaghdour@nyu.edu
We thank the children for their contribution to the study by providing blood samples and their families who agreed to be part of the study. We also acknowledge the effort of all the nurses and team at the CNRFP who assisted in sample collection in Burkina Faso. We thank the NYUAD Center for Genomics and Systems Biology Core Bioinformatics and Technology platforms for providing technical assistance and Jane Carlton for supporting our research program. This work was funded by NYUAD grant ADHPG AD105 to Y.I.
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