Functional deficit of T regulatory cells in Fulani, an ethnic group with low susceptibility to Plasmodium falciparum malaria

Previous interethnic comparative studies on the susceptibility to malaria performed in West Africa showed that Fulani are more resistant to Plasmodium falciparum malaria than are sympatric ethnic groups. This lower susceptibility is not associated to classic malaria-resistancegenes,andtheanalysisoftheimmuneresponse to P. falciparum sporozoite and blood stage antigens, as well as non-malariaantigens,revealedhigherimmunereactivityinFulani. Inthepresentstudywecomparedtheexpressionprofileofapanel of genes involved in immune response in peripheral blood mononuclearcells(PBMC)fromFulaniandsympatricMossifromBurkina Faso. An increased expression of T helper 1 (TH1)-related genes (IL-18, IFNG, and TBX21) and TH2-related genes (IL-4 and GATA3) and a reduced expression of genes distinctive of T regulatory activity (CTLA4 and FOXP3) were observed in Fulani. Microarray analysis on RNA from CD4+CD25+ (T regulatory) cells, performed with a panel of cDNA probes specific for 96 genes involved in immune modulation, indicated obvious differences between the two ethnic groups with 23% of genes, including TGFB, TGFBRs, CTLA4, and FOXP3, less expressed in Fulani compared with Mossi and European donors not exposed to malaria. As further indicationsofalowTregulatorycellactivity,Fulanishowedlowerserum levels of TGFbeta and higher concentrations of the proinflammatory chemokines CXCL10 and CCL22 compared with Mossi; moreover, the proliferative response of Fulani to malaria antigens was not affected by the depletion of CD25+ regulatory cells whereas that of Mossi was significantly increased. The results suggest that the higher resistance to malaria of the Fulani could derive from a functional deficit of T regulatory cells.