Bafica Aline Michelle Barbosa, Cardoso Luciana Santos, Oliveira Sérgio Costa, Loukas Alex, Góes Alfredo, Oliveira Ricardo Riccio, Carvalho Edgar M, Araujo Maria Ilma
Serviço de Imunologia, Complexo Hospitalar Universitário Professor Edgard Santos, Universidade Federal da Bahia, 5 Rua João das Botas s/n, Canela, 40110-160 Salvador, BA, Brazil.
J Parasitol Res. 2012;2012:520308. doi: 10.1155/2012/520308. Epub 2012 Nov 13.
High levels of proinflammatory cytokines such as IFN-γ and TNF are associated with tissue lesions in cutaneous leishmaniasis (CL). We previously demonstrated that Schistosoma mansoni antigens downmodulate the in vitro cytokine response in CL. In the current study we evaluated whether S. mansoni antigens alter monocyte and T-lymphocyte phenotypes in leishmaniasis. Peripheral blood mononuclear cells of CL patients were cultured with L. braziliensis antigen in the presence or absence of the S. mansoni antigens rSm29, rSmTSP-2- and PIII. Cells were stained with fluorochrome conjugated antibodies and analyzed by flow cytometry. The addition of rSm29 to the cultures decreased the expression of HLA-DR in nonclassical (CD14(+)CD16(++)) monocytes, while the addition of PIII diminished the expression of this molecule in classical (CD14(++)CD16(-)) and intermediate (CD14(++)CD16(+)) monocytes. The addition of PIII and rSmTSP-2 resulted in downmodulation of CD80 expression in nonclassical and CD86 expression in intermediate monocytes, respectively. These two antigens increased the expression of CTLA-4 in CD4(+) T cells and they also expanded the frequency of CD4(+)CD25(high)Foxp3(+) T cells. Taken together, we show that S. mansoni antigens, mainly rSmTSP-2 and PIII, are able to decrease the activation status of monocytes and also to upregulate the expression of modulatory molecules in T lymphocytes.
高水平的促炎细胞因子如干扰素-γ和肿瘤坏死因子与皮肤利什曼病(CL)中的组织损伤有关。我们之前证明曼氏血吸虫抗原可下调CL中的体外细胞因子反应。在当前研究中,我们评估了曼氏血吸虫抗原是否会改变利什曼病中单核细胞和T淋巴细胞的表型。将CL患者的外周血单核细胞与巴西利什曼原虫抗原一起培养,同时存在或不存在曼氏血吸虫抗原rSm29、rSmTSP-2和PIII。用荧光染料偶联抗体对细胞进行染色,并通过流式细胞术进行分析。向培养物中添加rSm29可降低非经典(CD14(+)CD16(++))单核细胞中HLA-DR的表达,而添加PIII可降低经典(CD14(++)CD16(-))和中间型(CD14(++)CD16(+))单核细胞中该分子的表达。添加PIII和rSmTSP-2分别导致非经典单核细胞中CD80表达下调和中间型单核细胞中CD86表达下调。这两种抗原增加了CD4(+) T细胞中CTLA-4的表达,并且它们还扩大了CD4(+)CD25(high)Foxp3(+) T细胞的频率。综上所述,我们表明曼氏血吸虫抗原,主要是rSmTSP-2和PIII,能够降低单核细胞的激活状态,并上调T淋巴细胞中调节分子的表达。