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首页> 外文期刊>Parasitology >The involvement of TLR2 in cytokine and reactive oxygen species (ROS) production by PBMCs in response to Leishmania major phosphoglycans (PGs).
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The involvement of TLR2 in cytokine and reactive oxygen species (ROS) production by PBMCs in response to Leishmania major phosphoglycans (PGs).

机译:TLR2参与PBMC对利什曼原虫主要磷酸聚糖(PGs)的反应所产生的细胞因子和活性氧(ROS)。

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摘要

In the present study, we show for the first time that lipophosphoglycan (LPG) stimulated cytokine production by human peripheral blood mononuclear cells is also mediated via Toll-like receptor (TLR2). In addition, in order to verify if TLR2 is involved in recognition of the purified PGs, neutralizing mAbs against TLR2 and TLR4 were used to treat the cells before being stimulated with PGs. We found strong Th1-promoting cytokines induced by sLPG but not by mLPG which was blocked by presence of anti-TLR2 mAb. This finding reveals a mechanism by which the first encounter and recognition of L. major promastigotes by mLPG after interaction with TLR2 provides a cytokine milieu for consequent Th2 differentiation. Moreover, having shown the strong induction of Th1-promoting cytokines and low production of IL-10 in response to sLPG might have vaccine implication since it is recognized by TLR2 providing signals to professional antigen presenting cells that reside in the skin to promote effective T cell responses against Leishmania infection. In addition, it was shown that purified mLPG and sLPG activate reactive oxygen species (ROS) production which is also blocked by anti-TLR2 but not by anti-TLR4. However, no inhibition was seen in PPG-induced cytokine and ROS production in the presence of anti-TLR2 and anti-TLR4, implying involvement of other receptors.
机译:在本研究中,我们首次显示脂环磷酰胺(LPG)刺激人外周血单核细胞产生的细胞因子也通过Toll样受体(TLR2)介导。此外,为了验证TLR2是否参与了纯化PG的识别,在被PG刺激之前,使用了针对TLR2和TLR4的中和mAb处理细胞。我们发现由sLPG诱导的强Th1促进细胞因子,但不受抗TLR2 mAb阻断的mLPG诱导。该发现揭示了一种机制,通过该机制,在与TLR2相互作用后,mLPG首次接触并识别了mLPG对主要前鞭毛乳杆菌的作用,为随后的Th2分化提供了细胞因子环境。而且,已经显示出强烈刺激Th1的细胞因子的诱导和对sLPG的IL-10的低产量可能具有疫苗意义,因为它已被TLR2识别,向驻留在皮肤中的专业抗原呈递细胞提供信号,从而促进有效的T细胞。对利什曼原虫感染的反应。另外,已经表明,纯化的mLPG和sLPG激活了活性氧(ROS)的产生,活性氧也被抗TLR2而不是抗TLR4阻断。但是,在存在抗TLR2和抗TLR4的情况下,在PPG诱导的细胞因子和ROS产生中未见抑制作用,这暗示了其他受体的参与。

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