Torcia Maria G, Santarlasci Veronica, Cosmi Lorenzo, Clemente AnnMaria, Maggi Laura, Mangano Valentina D, Verra Federica, Bancone Germana, Nebie Issa, Sirima Bienvenu Sodiomon, Liotta Francesco, Frosali Francesca, Angeli Roberta, Severini Carlo, Sannella Anna R, Bonini Paolo, Lucibello Maria, Maggi Enrico, Garaci Enrico, Coluzzi Mario, Cozzolino Federico, Annunziato Francesco, Romagnani Sergio, Modiano David
Department of Clinical Physiopathology, University of Firenze, Viale Pieraccini 6, 50139 Firenze, Italy.
Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):646-51. doi: 10.1073/pnas.0709969105. Epub 2008 Jan 3.
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.
先前在西非进行的关于疟疾易感性的种族间比较研究表明，富拉尼人比同域的其他种族对恶性疟原虫疟疾更具抵抗力。这种较低的易感性与经典的疟疾抗性基因无关，对恶性疟原虫子孢子和血期抗原以及非疟疾抗原的免疫反应分析显示，富拉尼人的免疫反应性更高。在本研究中，我们比较了来自布基纳法索的富拉尼人和同域的莫西人外周血单核细胞（PBMC）中一组参与免疫反应的基因的表达谱。在富拉尼人中观察到辅助性T细胞1（TH1）相关基因（IL-18、IFNγ和TBX21）和TH2相关基因（IL-4和GATA3）的表达增加，而调节性T细胞活性特异基因（CTLA4和FOXP3）的表达减少。对CD4+CD25+（调节性T）细胞的RNA进行微阵列分析，使用一组针对96个参与免疫调节的基因的cDNA探针，结果表明这两个种族之间存在明显差异，与莫西人和未接触疟疾的欧洲供体相比，富拉尼人中23%的基因（包括TGFβ、TGFβR、CTLA4和FOXP3）表达较低。作为调节性T细胞活性较低的进一步迹象，与莫西人相比，富拉尼人的血清TGFβ水平较低，促炎趋化因子CXCL10和CCL22浓度较高；此外，富拉尼人对疟疾抗原的增殖反应不受CD25+调节性细胞耗竭的影响，而莫西人的增殖反应则显著增加。结果表明，富拉尼人对疟疾的较高抵抗力可能源于调节性T细胞的功能缺陷。
