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.

Highlights

  • The Fulani ethnic group has relatively better protection from Plasmodium falciparum malaria than other ethnic groups living alongside them in West Africa

  • Due to the 2014 West African Ebola outbreak and local political unrest, the collection was delayed until the end of the July-October high transmission season, to November 2014

  • As the levels of IL-1b and IL-18 are relatively low in blood plasma, we examined the levels of suppressors of inflammasome signaling, including IL-1 receptor antagonist (IL-1Ra), the soluble decoy IL-1 receptor, type II (IL-1RII), and decoy receptor IL-18 binding protein (IL-18BP), which have effective concentrations several orders of magnitude higher their target cytokines (Boraschi and Tagliabue, 2013)

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Summary

Introduction

The Fulani ethnic group has relatively better protection from Plasmodium falciparum malaria than other ethnic groups living alongside them in West Africa. Since the first report of the different response of Fulani to P.falciparum in 1996 (Modiano et al, 1996), populations of Fulani living sympatrically with other ethnic groups from Mali to as far east as Sudan, have consistently been reported to have fewer symptomatic cases of malaria, lower P.falciparum infection rates, and lower P.falciparum density in infected individuals (Arama et al, 2015a). The basis for the lower susceptibility of Fulani to malaria is yet to be established. The incidence of these classic malaria resistance genes are lower in

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