View in EDS

Single-cell transcriptomics reveals inter-ethnic variation in immune response to Falciparum malaria

Saved in:
Bibliographic Details
Title: Single-cell transcriptomics reveals inter-ethnic variation in immune response to Falciparum malaria
Authors: Shahin, Tala, Jurkovic, Jakub, Dieng, Mame, Manikandan, Vinu, Abdrabou, Wael, Alamad, Bana, Bayaraa, Odmaa, Diawara, Aïssatou, Sermé, Samuel Sindié, Henry, Noëlie Béré, Sombie, Salif, Almojil, Dareen, Arnoux, Marc, Drou, Nizar, Soulama, Issiaka, Idaghdour, Youssef
Contributors: NYU Abu Dhabi - New York University Abu Dhabi
Source: Am J Hum Genet
Publisher Information: Elsevier BV, 2025.
Publication Year: 2025
Subject Terms: Male, Mossi, Leukocytes, Mononuclear/metabolism, Malaria, Falciparum/immunology, Fulani, malaria, Genetics & genetic processes, immune response, Génétique & processus génétiques, Ethnicity/genetics, Monocytes/metabolism, Report, Burkina Faso, Genetics, Humans, Leukocytes, Mononuclear/immunology, Child, Genetics (clinical), Leukocytes, Mononuclear/parasitology, single-cell RNA-seq, Gene Expression Profiling, Plasmodium falciparum/genetics, Monocytes/immunology, Malaria, Falciparum/genetics, Life sciences, sc-eQTL, Child, Preschool, African genomics, Sciences du vivant, Female, Single-Cell Analysis, Transcriptome, Malaria, Falciparum/parasitology
Description: 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.
Document Type: Article
Other literature type
Language: English
ISSN: 0002-9297
DOI: 10.1016/j.ajhg.2025.01.020
Access URL: https://pubmed.ncbi.nlm.nih.gov/39970911
Rights: CC BY NC ND
Accession Number: edsair.doi.dedup.....3342e23c2e6a8871a814ba68e15e9deb
Database: OpenAIRE
Description
Abstract: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.
ISSN:00029297
DOI:10.1016/j.ajhg.2025.01.020