Major transcriptional changes observed in the Fulani, an ethnic group less susceptible to malaria

Abstract

The Fulani ethnic group has relatively better protection from Plasmodium falciparum malaria, as reflected by fewer symptomatic cases of malaria, lower infection rates, and lower parasite densities compared to sympatric ethnic groups. However, the basis for this lower susceptibility to malaria by the Fulani is unknown. The incidence of classic malaria resistance genes are lower in the Fulani than in other sympatric ethnic populations, and targeted SNP analyses of other candidate genes involved in the immune response to malaria have not been able to account for the observed difference in the Fulani susceptibility to P.falciparum. Therefore, we have performed a pilot study to examine global transcription and DNA methylation patterns in specific immune cell populations in the Fulani to elucidate the mechanisms that confer the lower susceptibility to P.falciparum malaria. When we compared uninfected and infected Fulani individuals, in contrast to uninfected and infected individuals from the sympatric ethnic group Mossi, we observed a key difference: a strong transcriptional response was only detected in the monocyte fraction of the Fulani, where over 1000 genes were significantly differentially expressed upon P.falciparum infection.

Seroreactivity of Populations Living in Endemic Area of Burkina Faso to Plasmodium falciparum Alpha-Helical Coiled Coil Proteins Motifs by Protein Microarray

“…The findings of that study showed that the Fulani groups had a low prevalence of these genes compared to the sympatric groups [19,20]. More recently, a study conducted in the same communities showed that transcriptional changes were observed in Fulani and could explain the lower susceptibility to malaria infection of this group compared to that of other populations [20]. We have also investigated the influence of hemoglobin in the acquisition of the immunity to the antigens used in our study.…”

“…Genetic studies based on some classical genes that confer resistance to malaria were explored to understand the high response of Fulani compared to the sympatric ethnic groups. The findings of that study showed that the Fulani groups had a low prevalence of these genes compared to the sympatric groups [19,20]. More recently, a study conducted in the same communities showed that transcriptional changes were observed in Fulani and could explain the lower susceptibility to malaria infection of this group compared to that of other populations [20].…”

Transcriptomic Studies of Malaria: a Paradigm for Investigation of Systemic Host-Pathogen Interactions

“…It is tempting to speculate that this may indicate that none of these individuals had reached sufficient parasitemia to trigger a response and that the set points for such a response may differ between malaria-experienced and previously naive individuals. This concept may be supported by data from a recent study comparing the transcriptional responses of asymptomatic adolescent men from two sympatric ethnic groups in Burkina Faso with similar peripheral blood parasite densities ( 163 ). Comparison of purified monocyte transcriptomes between 7 uninfected and 2 infected individuals of the Fulani tribe showed dramatic differences in gene expression, whereas the same comparison for individuals of the Mossi tribe showed negligible differences.…”

Disrupting the Code: Epigenetic Dysregulation of Lymphocyte Function during Infectious Disease and Lymphoma Development

“…3). Freshly isolated monocytes and lymphocytes from different African ethnic groups naturally infected with P. falciparum revealed that this hyperresponsiveness is correlated with increased H3K4me3 marks at important proinflammatory promoters, such as IFN, TNF, IL6, IL18, and TGFB1 genes, compared with healthy controls (81). This altered cytokine microenvironment influences the adaptive immune response of the infected host, leading to the chronic features of this infection.…”