Journal Article

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

Mangano, Valentina D, Liotta, Francesco, Maggi, Enrico, Annunziato, Francesco, Bancone, Germana, Sirima, Bienvenu Sodiomon, Cozzolino, Federico, Frosali, Francesca, Clemente, AnnMaria, Verra, Federica, Modiano, David, Lucibello, Maria, Garaci, Enrico, Romagnani, Sergio, Angeli, Roberta, Bonini, Paolo, Severini, Carlo, Nebie, Issa, Maggi, Laura, Torcia, Maria G, Santarlasci, Veronica, Sannella, Anna R, Cosmi, Lorenzo, Coluzzi, Mario

2008

Overview

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-resistance genes, and the analysis of the immune response to P. falciparum sporozoite and blood stage antigens, as well as non-malaria antigens, revealed higher immune reactivity in Fulani. In the present study we compared the expression profile of a panel of genes involved in immune response in peripheral blood mononuclear cells (PBMC) from Fulani and sympatric Mossi from Burkina Faso. An increased expression of T helper 1 (TH1)-related genes (IL-18, IFNγ, 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 TGFβ, TGFβRs, CTLA4, and FOXP3, less expressed in Fulani compared with Mossi and European donors not exposed to malaria. As further indications of a low T regulatory cell activity, Fulani showed lower serum levels of TGFβ 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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Adult / Animals / Antigens / Biological Sciences / blood serum / Burkina Faso / CD4-positive T-lymphocytes / CD4-Positive T-Lymphocytes - parasitology / Cell growth / Cell Proliferation / Cells / chemokine CCL22 / chemokine CXCL10 / Comparative studies / complementary DNA / Cytokines / Ethnic groups / Ethnicity / Female / GATA transcription factors / Gene expression / Genes / Genetic Predisposition to Disease / Humans / Immune response / Immune System / Infections / interleukin-18 / Interleukin-2 Receptor alpha Subunit - biosynthesis / interleukin-4 / Leukocytes, Mononuclear - parasitology / Malaria / Malaria, Falciparum - ethnology / Malaria, Falciparum - genetics / Malaria, Falciparum - parasitology / Male / Mali / microarray technology / Middle Aged / Minority & ethnic groups / nationalities and ethnic groups / Plasmodium falciparum / Plasmodium falciparum - metabolism / Proteins / RNA / T cell receptors / T lymphocytes / T-Lymphocytes, Regulatory - parasitology / transforming growth factor beta / Vector-borne diseases