Progesterone Can Directly Inhibit the Life Activities of Toxoplasma gondii In Vitro through the Progesterone Receptor Membrane Component (PGRMC).

Progesterone Can Directly Inhibit the Life Activities of Toxoplasma gondii In Vitro through the Progesterone Receptor Membrane Component (PGRMC).
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黄体酮可通过黄体酮受体膜成分(PGRMC)直接抑制体外弓形虫的生命活动

DOI:
10.3390/ijms23073843
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发表时间:
2022-03-31
影响因子:
5.6
通讯作者:
Liu Q
Liu Q
中科院分区:
生物学2区
文献类型:
--
作者:
Wu Y;Zhang X;Fu Y;Liu J;Xue Y;Liu Q

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刚地弓形虫(弓形虫)是一种条件致病菌,对怀孕动物和人都有特殊的致病作用。孕酮(P4)是一种支持妊娠的关键激素,其水平在妊娠早期自然波动。然而,宿主P4水平与弓形虫传染性和致病性的关系尚不清楚。我们的研究表明,P4显著抑制速殖子的侵袭和增殖,导致体外细胞骨架子芽和随后的自噬异常。为了研究其潜在的机制,我们鉴定了一个定位于线粒体的弓形虫孕酮膜受体蛋白(TgPGRMC),该蛋白与P4对速殖子的作用密切相关。pgrmc基因的敲除使P4抑制作用产生抗性。我们的研究结果在体外证明了P4单因子与弓形虫之间的直接关系,并表明TgPGRMC是弓形虫与P4之间的重要纽带,为妊娠期弓形虫感染的研究提供了新的方向。
Toxoplasma gondii (T. gondii), as an opportunistic pathogen, has special pathogenic effects on pregnant animals and humans. Progesterone (P4) is a critical hormone that supports pregnancy, and its levels fluctuate naturally during early pregnancy. However, little is known about the association of host P4 levels with the infectivity and pathogenicity of T. gondii. Our study showed that P4 significantly inhibited the invasion and proliferation of tachyzoites, resulting in abnormal cytoskeletal daughter budding and subsequent autophagy in vitro. To investigate the underlying mechanism, we identified a Toxoplasma gondii progesterone membrane receptor protein (TgPGRMC) that was localized to the mitochondrion and closely related to the effect of P4 on tachyzoites. The knockout of the pgrmc gene conferred resistance to P4 inhibitory effects. Our results prove the direct relationship between P4 single factors and T. gondii in vitro and demonstrate that TgPGRMC is an important link between T. gondii and P4, providing a new direction for research on T. gondii infection during pregnancy.
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