National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Int J Mol Sci. 2022 Mar 31;23(7):3843. doi: 10.3390/ijms23073843.
, 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 . 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 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 gene conferred resistance to P4 inhibitory effects. Our results prove the direct relationship between P4 single factors and in vitro and demonstrate that TgPGRMC is an important link between and P4, providing a new direction for research on infection during pregnancy.
刚地弓形虫作为一种机会致病寄生虫，对妊娠动物和人类具有特殊的致病作用。孕激素（P4）是一种支持妊娠的关键激素，其水平在妊娠早期会自然波动。然而，宿主 P4 水平与刚地弓形虫的感染力和致病性之间的关系知之甚少。我们的研究表明，P4 显著抑制速殖子的侵袭和增殖，导致体外异常细胞骨架子细胞芽生和随后的自噬。为了探究其潜在机制，我们鉴定了一个孕激素膜受体蛋白（TgPGRMC），该蛋白定位于线粒体，与 P4 对速殖子的作用密切相关。该基因的敲除赋予了对 P4 抑制作用的抗性。我们的结果证明了 P4 单因素与体外弓形虫之间的直接关系，并表明 TgPGRMC 是弓形虫与 P4 之间的重要联系，为妊娠期间弓形虫感染的研究提供了新的方向。
