PDZ protein interacting specifically with Tc10 or PIST is a mammalian trans-Golgi resident protein that regulates subcellular sorting of plasma membrane receptors. PIST has recently emerged as a key player in regulating viral pathogenesis. Nevertheless, the involvement of PIST in parasitic infections remains unexplored. Leishmania parasites infiltrate their host macrophage cells through phagocytosis, where they subsequently multiply within the parasitophorous vacuole (PV). Host cell autophagy has been found to be important in regulating this parasite infection. Since PIST plays a pivotal role in triggering autophagy through the Beclin 1–PI3KC3 pathway, it becomes interesting to identify the status of PIST during Leishmania infection. We found that while macrophage cells are infected with Leishmania major (L. major), the expression of PIST protein remains unaltered; however, it traffics from the Golgi compartment to PV. Further, we identified that in L. major-infected macrophage cells, PIST associates with the autophagy regulatory protein Beclin 1 within the PVs; however, PIST does not interact with LC3. Reduction in PIST protein through siRNA silencing significantly increased parasite burden, whereas overexpression of PIST in macrophages restricted L. major infectivity. Together, our study reports that the macrophage PIST protein is essential in regulating L. major infectivity.

中文翻译：

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巨噬细胞 PIST 蛋白在调节利什曼原虫重大感染中的作用

PDZ 蛋白与 Tc10 或 PIST 特异性相互作用，是一种哺乳动物跨高尔基体驻留蛋白，可调节质膜受体的亚细胞排序。 PIST 最近已成为调节病毒发病机制的关键角色。然而，PIST 与寄生虫感染的关系仍有待探索。利什曼原虫寄生虫通过吞噬作用渗入宿主巨噬细胞，随后在寄生液泡 (PV) 内繁殖。人们发现宿主细胞自噬对于调节这种寄生虫感染非常重要。由于 PIST 在通过 Beclin 1-PI3KC3 途径触发自噬中发挥着关键作用，因此识别利什曼原虫感染期间 PIST 的状态变得很有趣。我们发现，虽然巨噬细胞被大型利什曼原虫（L.major）感染，但PIST蛋白的表达保持不变；然而，它从高尔基室流向PV。此外，我们还发现，在L. Major感染的巨噬细胞中，PIST 与 PV 内的自噬调节蛋白 Beclin 1 相关。然而，PIST 不与 LC3 相互作用。通过 siRNA 沉默减少 PIST 蛋白显着增加寄生虫负担，而巨噬细胞中 PIST 的过度表达限制了L.major 的感染性。总之，我们的研究报告称，巨噬细胞 PIST 蛋白对于调节大型利斯特菌感染性至关重要。