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A novel receptor for platelet-activating factor and lysophosphatidylcholine in Trypanosoma cruzi
Molecular Microbiology ( IF 3.6 ) Pub Date : 2021-06-29 , DOI: 10.1111/mmi.14778
Felipe S Coelho 1 , Mauricio M Oliveira 2 , Danielle P Vieira 3 , Pedro H M Torres 4 , Isabel C F Moreira 1 , Erica S Martins-Duarte 5 , Inês C Gonçalves 1 , Adriana Cabanelas 1 , Pedro G Pascutti 4 , Stenio P Fragoso 6 , Angela H Lopes 1
Affiliation  

The lipid mediators, platelet-activating factor (PAF) and lysophosphatidylcholine (LPC), play relevant pathophysiological roles in Trypanosoma cruzi infection. Several species of LPC, including C18:1 LPC, which mimics the effects of PAF, are synthesized by T. cruzi. The present study identified a receptor in T. cruzi, which was predicted to bind to PAF, and found it to be homologous to members of the progestin and adiponectin family of receptors (PAQRs). We constructed a three-dimensional model of the T. cruzi PAQR (TcPAQR) and performed molecular docking to predict the interactions of the TcPAQR model with C16:0 PAF and C18:1 LPC. We knocked out T. cruzi PAQR (TcPAQR) gene and confirmed the identity of the expressed protein through immunoblotting and immunofluorescence assays using an anti-human PAQR antibody. Wild-type and knockout (KO) parasites were also used to investigate the in vitro cell differentiation and interactions with peritoneal mouse macrophages; TcPAQR KO parasites were unable to react to C16:0 PAF or C18:1 LPC. Our data are highly suggestive that PAF and LPC act through TcPAQR in T. cruzi, triggering its cellular differentiation and ability to infect macrophages.

中文翻译:

克氏锥虫中血小板活化因子和溶血磷脂酰胆碱的新受体

脂质介质、血小板活化因子 (PAF) 和溶血磷脂酰胆碱 (LPC) 在克氏锥虫感染中起相关的病理生理学作用。T. cruzi合成了几种 LPC,包括模拟 PAF 效果的 C18:1 LPC 。本研究确定了T. cruzi中的一种受体,预计该受体与 PAF 结合,并发现它与孕激素和脂联素受体家族 (PAQRs) 的成员同源。我们构建了T. cruzi PAQR (TcPAQR)的三维模型并进行分子对接以预测 TcPAQR 模型与 C16:0 PAF 和 C18:1 LPC 的相互作用。我们击倒了T. cruziPAQR (TcPAQR) 基因,并使用抗人 PAQR 抗体通过免疫印迹和免疫荧光测定证实了表达蛋白质的身份。野生型和敲除(KO)寄生虫也用于研究体外细胞分化和与腹膜小鼠巨噬细胞的相互作用;TcPAQR KO 寄生虫无法对 C16:0 PAF 或 C18:1 LPC 作出反应。我们的数据高度暗示 PAF 和 LPC 通过T. cruzi中的 TcPAQR 起作用,触发其细胞分化和感染巨噬细胞的能力。
更新日期:2021-06-29
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