NEW YORK – Susceptibility to the malaria-causing parasite Plasmodium falciparum may differ between the Fulani and Mossi ethnic groups in West Africa because of distinct immune cell gene expression and gene regulatory features, according to new research.
"Differences in malaria susceptibility among populations are documented, but the underlying mechanisms remain poorly understood," senior and corresponding author Youssef Idaghdour, a researcher affiliated with New York University and NYU Abu Dhabi, and his colleagues wrote in a paper published in the American Journal of Human Genetics on Tuesday, noting that "the Fulani ethnic group in Africa is less susceptible to malaria compared to other sympatric groups, such as the Mossi."
Using single-cell RNA sequencing, the researchers profiled transcriptomic patterns in more than 70,000 peripheral blood mononuclear cells (PBMCs) isolated from blood samples for 126 Fulani and Mossi children from rural Burkina Faso, including 87 children with a history of malaria infection and 39 uninfected children.
The team uncovered 30 cell subtypes by clustering the scRNA-seq data and went on to highlight subtype-specific gene expression differences between the two ethnic groups. They included malaria susceptibility-related expression shifts in monocytes, CD4-positive T cells, CD8-positive T cells, and natural killer cells, as well as pathways involved in B cell activation.
In addition, the team saw signs that the less malaria-susceptible Fulani population tended to have enhanced B-cell subtype activation and lower-than-usual levels of pro-inflammatory and inflammatory pathway activity — findings the investigators explored further with expression quantitative trait locus (eQTL) analyses that brought in participants' genotyping data to focus on gene regulation in CD14-positive and CD16-positive monocytes.
"Our analysis identified 120 and 71 cis-eQTLs, as well as 54 and 71 gene-by-ethnicity effects for CD14-positive and CD16-positive monocytes, respectively, that were detected only in one of the two ethnic groups," the authors reported, noting that immune genes such as CD36 and MT2A were among the differentially expressed genes detected.
"Our findings indicate that Fulani children's monocytes establish a basal immunoregulatory state, suggesting an inherent priming of their immune system to modulate inflammatory responses and mitigate malarial pathogenesis," the authors suggested, adding that these and other differences in activity involving other immune cell types such as T cells, natural killer cells, and memory B cells appeared to collectively protect against malaria.
Together, they argued, the current work "underscores the need for further investigations into specific components of the Fulani diet that could be influencing the observed divergent inter-ethnic transcriptional signatures, potentially contributing to variations in malaria susceptibility across populations."