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首页> 外文期刊>Apoptosis >Toxoplasma gondii Dense Granule Antigen 1 stimulates apoptosis of monocytes through autocrine TGF-β signaling
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Toxoplasma gondii Dense Granule Antigen 1 stimulates apoptosis of monocytes through autocrine TGF-β signaling

机译：弓形虫致密颗粒抗原1通过自分泌TGF-β信号刺激单核细胞凋亡

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摘要

Monocyte/macrophages represent the first line of defense against protozoan parasites. Different mechanisms of monocyte suppression by Toxoplasma gondii that sustain parasite invasion and persistence have been described, including apoptosis. In the present study, we investigated the effect of microbial excretory–secretory polypeptides, namely the microneme protein MIC3 and the dense granule antigen GRA1, on apoptosis of monocytes from patients with congenital toxoplasmosis and healthy individuals. We found that GRA1 but not MIC3 could induce apoptosis of monocytes, observing the effect in samples from both Toxoplasma-infected and uninfected individuals, thus ruling out involvement of mechanisms of apoptosis linked to adaptive immunity or a cellular context related to infection. Selective inhibition of TGF-β type I receptors reversed GRA1-induced apoptosis, indicating that this apoptosis involved canonical TGF-β signaling. By using TGF-β-neutralizing antibodies, we showed that monocyte apoptosis required endogenous TGF-β and that GRA1 stimulation activated TGF-β transcription and expression in monocytes but not lymphocytes, suggesting involvement of an autocrine TGF-β-mediated mechanism in GRA1-induced apoptosis.
机译：单核细胞/巨噬细胞代表针对原生动物寄生虫的第一道防线。已经描述了弓形虫抑制单轴细胞维持寄生虫侵袭和持久性的不同机制，包括细胞凋亡。在本研究中，我们研究了微生物排泄-分泌多肽，即微nemene蛋白MIC3和致密颗粒抗原GRA1，对先天性弓形虫病患者和健康个体单核细胞凋亡的影响。我们发现，GRA1而非MIC3可以诱导单核细胞凋亡，观察弓形虫感染和未感染个体的样本中的作用，从而排除了与适应性免疫或感染相关的细胞环境相关的凋亡机制的参与。 TGF-βI型受体的选择性抑制逆转了GRA1诱导的细胞凋亡，表明该细胞凋亡涉及正常的TGF-β信号传导。通过使用TGF-β中和抗体，我们发现单核细胞凋亡需要内源性TGF-β，并且GRA1刺激激活了TGF-β在单核细胞而非淋巴细胞中的转录和表达，表明GRA1-参与了自分泌TGF-β介导的机制。诱导细胞凋亡。

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