College of Life Sciences, Southwest Forestry University, Kunming, China.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Front Cell Infect Microbiol. 2024 Jan 11;13:1336600. doi: 10.3389/fcimb.2023.1336600. eCollection 2023.
is an obligate intracellular bacterium that causes Q fever, a zoonotic disease typically manifests as a severe flu-illness. After invading into the host cells, delivers effectors to regulate the vesicle trafficking and fusion events to form a large and mature -containing vacuole (CCV), providing sufficient space and nutrition for its intracellular growth and proliferation. Lysosomal trafficking regulator (LYST) is a member of the Beige and Chediak-Higashi syndrome (BEACH) family, which regulates the transport of vesicles to lysosomes and regulates TLR signaling pathway, but the effect of LYST on infection is unclear. In this study, a series of experiments has been conducted to investigate the influence of LYST on intracellular growth of . Our results showed that transcription was up-regulated in the host cells after infection, but there is no significant change in expression level after infection with the Dot/Icm type IV secretion system (T4SS) mutant strain, while CCVs expansion and significantly increasing load of appeared in the host cells with a silenced gene, suggesting LYST inhibits the intracellular proliferation of by reducing CCVs size. Then, the size of CCVs and the load of in the HeLa cells pretreated with E-64d were significantly decreased. In addition, the level of iNOS was decreased significantly in LYST knockout THP-1 cells, which was conducive to the intracellular replication of . This data is consistent with the phenotype of L-NMMA-treated THP-1 cells infected with . Our results revealed that the upregulation of transcription after infection is due to effector secretion of and LYST inhibit the intracellular replication of by reducing the size of CCVs and inducing expression.
是一种专性细胞内细菌,可引起 Q 热,这是一种人畜共患疾病,通常表现为严重的流感样疾病。进入宿主细胞后,会输送效应物来调节囊泡运输和融合事件,形成一个含有大量成熟的空泡(CCV),为其在细胞内的生长和增殖提供足够的空间和营养。溶酶体运输调节剂(LYST)是 Beige 和 Chediak-Higashi 综合征(BEACH)家族的成员,调节囊泡向溶酶体的运输,并调节 TLR 信号通路,但 LYST 对的感染的影响尚不清楚。在这项研究中,进行了一系列实验来研究 LYST 对细胞内生长的影响。我们的结果表明,感染后宿主细胞中的转录上调,但感染 Dot/Icm 型 IV 型分泌系统(T4SS)突变株后,表达水平没有明显变化,而 CCVs 扩张和明显增加的负荷出现在沉默基因的宿主细胞中,表明 LYST 通过减少 CCVs 的大小来抑制的细胞内增殖。然后,用 E-64d 预处理的 HeLa 细胞中的 CCVs 大小和的负荷明显减少。此外,LYST 缺失的 THP-1 细胞中 iNOS 的水平明显降低,有利于的细胞内复制。这一数据与用处理的 THP-1 细胞感染后的表型一致。我们的结果表明,感染后转录的上调是由于的效应物分泌,而 LYST 通过减少 CCVs 的大小并诱导的表达来抑制的细胞内复制。