美洲皮肤利什曼病:在近期患有活动性疾病的患者中,Th1和Treg介质的mRNA表达占主导地位。

American tegumentary leishmaniasis: mRNA expression for Th1 and Treg mediators are predominant in patients with recent active disease.

作者信息

Souza Marina A, Almeida Thays M, Castro Maria Carolina A B, Oliveira-Mendes Andresa P, Almeida Amanda F, Oliveira Beatriz C, Rocha Lucas F, Medeiros Angela C R, Brito Maria E F, Dessein Alain J J, Pereira Valéria R A

机构信息

Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil.

Hospital Universitário Oswaldo Cruz, Universidade de Pernambuco (HUOC/UPE), Brazil.

出版信息

Immunobiology. 2016 Feb;221(2):253-9. doi: 10.1016/j.imbio.2015.08.009. Epub 2015 Aug 14.

Abstract

Besides the Th1×Th2 paradigm, Treg and Th17 cytokines may play a role in the response to American tegumentary leishmaniasis. Considering the sensitivity and accuracy of qPCR and the lack of studies using this approach, we evaluated mRNA expression for IFN-γ, TNF-α, IL-4, IL-10, IL-6, IL-17A, IL-22, TGF-β, Foxp3 and RORC in peripheral blood mononuclear cells (PBMC) from patients with active disease, after stimulation with L. (V.) braziliensis soluble or insoluble fractions. Our results show that the antigens promoted specific mRNA expression related to the immune response in patients with ATL, and the insoluble fraction seems to stimulate the immune response in a higher intensity. The pro-inflammatory response was also fueled by IFN-γ and TNF-α, probably due to the active disease. IL-4, in certain way, seems to regulate this response along with IL-10 that may be produced by Treg cells, which are supposedly present in the patients' samples due the evidenced expression of Foxp3, in the presence of AgIns. In contrast, down-regulated RORC suggests that the significant levels of IL-6 expressed in response to AgSol were not able to induce an expressive Th17 profile along with TGF-β, which might have predominantly contributed to the development of a regulatory profile in the active disease.

摘要

除了Th1×Th2模式外,调节性T细胞(Treg)和辅助性T细胞17(Th17)细胞因子可能在美洲皮肤利什曼病的反应中发挥作用。考虑到定量聚合酶链反应(qPCR)的敏感性和准确性以及缺乏使用这种方法的研究,我们评估了来自活动性疾病患者的外周血单个核细胞(PBMC)在受到巴西利什曼原虫(Viannia亚属)可溶性或不溶性组分刺激后,干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白细胞介素-4(IL-4)、白细胞介素-10(IL-10)、白细胞介素-6(IL-6)、白细胞介素-17A(IL-17A)、白细胞介素-22(IL-22)、转化生长因子-β(TGF-β)、叉头框蛋白3(Foxp3)和维甲酸相关孤儿受体C(RORC)的信使核糖核酸(mRNA)表达。我们的结果表明,这些抗原促进了与美洲皮肤利什曼病患者免疫反应相关的特异性mRNA表达,并且不溶性组分似乎以更高的强度刺激免疫反应。促炎反应也由IFN-γ和TNF-α推动,这可能归因于活动性疾病。IL-4似乎在一定程度上与可能由Treg细胞产生的IL-10一起调节这种反应,由于在存在不溶性抗原(AgIns)的情况下有Foxp3的表达证据,推测Treg细胞存在于患者样本中。相反,RORC表达下调表明,响应可溶性抗原(AgSol)而表达的显著水平的IL-6未能与TGF-β一起诱导明显的Th17细胞谱,这可能主要促成了活动性疾病中调节性细胞谱的发展。

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