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-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, IFNgamma, 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 TGFbeta, TGFbetaRs, 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 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.
Torcia
Maria G
MG
Department of Clinical Physiopathology, University of Firenze, Viale Pieraccini 6, 50139 Firenze, Italy. g.torcia@dfc.unifi.it
Santarlasci
Veronica
V
Cosmi
Lorenzo
L
Clemente
AnnMaria
A
Maggi
Laura
L
Mangano
Valentina D
VD
Verra
Federica
F
Bancone
Germana
G
Nebie
Issa
I
Sirima
Bienvenu Sodiomon
BS
Liotta
Francesco
F
Frosali
Francesca
F
Angeli
Roberta
R
Severini
Carlo
C
Sannella
Anna R
AR
Bonini
Paolo
P
Lucibello
Maria
M
Maggi
Enrico
E
Garaci
Enrico
E
Coluzzi
Mario
M
Cozzolino
Federico
F
Annunziato
Francesco
F
Romagnani
Sergio
S
Modiano
David
D
D000328:Adult; D000818:Animals; D002050:Burkina Faso; D015496:CD4-Positive T-Lymphocytes / Q000469:parasitology; D049109:Cell Proliferation; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007107:Immune System; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000469:parasitology; D016778:Malaria, Falciparum / Q000208:ethnology* / Q000235:genetics* / Q000469:parasitology*; D008297:Male; D008302:Mali; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000469:parasitology*
D053645:Interleukin-2 Receptor alpha Subunit