Metenou Simon, Dembélé Benoit, Konate Siaka, Dolo Housseini, Coulibaly Siaka Y, Coulibaly Yaya I, Diallo Abdallah A, Soumaoro Lamine, Coulibaly Michel E, Sanogo Dramane, Doumbia Salif S, Wagner Marissa, Traoré Sekou F, Klion Amy, Mahanty Siddhartha, Nutman Thomas B
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 2009 Jul 15;183(2):916-24. doi: 10.4049/jimmunol.0900257. Epub 2009 Jun 26.
The effect of filarial infections on malaria-specific immune responses was investigated in Malian villages coendemic for filariasis (Fil) and malaria. Cytokines were measured from plasma and Ag-stimulated whole blood from individuals with Wuchereria bancrofti and/or Mansonella perstans infections (Fil(+); n = 19) and those without evidence of filarial infection (Fil(-); n = 19). Plasma levels of IL-10 (geometric mean [GM], 22.8 vs 10.4) were higher in Fil(+) compared with Fil(-), whereas levels of IFN-inducible protein (IP)-10 were lower in Fil(+) (GM, 66.3 vs 110.0). Fil(+) had higher levels of spontaneously secreted IL-10 (GM, 59.3 vs 6.8 pg/ml) and lower levels of IL-2 (1.0 vs 1.2 pg/ml) than did Fil(-). Although there were no differences in levels of Staphylococcus aureus enterotoxin B-induced cytokines between the two groups, Fil(+) mounted lower IL-12p70 (GM, 1.11 vs 3.83 pg/ml; p = 0.007), IFN-gamma (GM, 5.44 vs 23.41 pg/ml; p = 0.009), and IP-10 (GM, 29.43 vs 281.7 pg/ml; p = 0.007) responses following malaria Ag (MalAg) stimulation compared with Fil(-). In contrast, Fil(+) individuals had a higher MalAg-specific IL-10 response (GM, 7318 pg/ml vs 3029 pg/ml; p = 0.006) compared with those without filarial infection. Neutralizing Ab to IL-10 (but not to TGFbeta) reversed the down-regulated MalAg-specific IFN-gamma and IP-10 (p < 0.001) responses in Fil(+). Together, these data demonstrate that filarial infections modulate the Plasmodium falciparum-specific IL-12p70/IFN-gamma secretion pathways known to play a key role in resistance to malaria and that they do so in an IL-10-dependent manner.
在同时流行丝虫病(Fil)和疟疾的马里村庄,研究了丝虫感染对疟疾特异性免疫反应的影响。对感染班氏吴策线虫和/或常现曼森线虫(Fil(+);n = 19)以及无丝虫感染证据(Fil(-);n = 19)的个体,检测了血浆和抗原刺激全血中的细胞因子。与Fil(-)相比,Fil(+)个体的血浆IL-10水平(几何均值[GM],22.8对10.4)更高,而干扰素诱导蛋白(IP)-10水平在Fil(+)中更低(GM,66.3对110.0)。与Fil(-)相比,Fil(+)个体自发分泌的IL-10水平更高(GM,59.3对6.8 pg/ml),IL-2水平更低(1.0对1.2 pg/ml)。尽管两组之间金黄色葡萄球菌肠毒素B诱导的细胞因子水平没有差异,但与Fil(-)相比,Fil(+)个体在疟疾抗原(MalAg)刺激后产生的IL-12p70(GM,1.11对3.83 pg/ml;p = 0.007)、IFN-γ(GM,5.44对23.41 pg/ml;p = 0.009)和IP-10(GM,29.43对281.7 pg/ml;p = 0.007)反应更低。相反,与无丝虫感染个体相比,Fil(+)个体的MalAg特异性IL-10反应更高(GM,7318 pg/ml对3029 pg/ml;p = 0.006)。用抗IL-10中和抗体(而非抗TGFβ中和抗体)可逆转Fil(+)个体中下调的MalAg特异性IFN-γ和IP-10反应(p < 0.001)。总之,这些数据表明,丝虫感染可调节已知在疟疾抗性中起关键作用的恶性疟原虫特异性IL-12p70/IFN-γ分泌途径,且是以IL-10依赖的方式进行调节。