{"title":"Toxoplasma gondii ROP17 promotes autophagy via the Bcl-2-Beclin 1 pathway.","authors":"Min Guo, Jia Sun, Wen-Tao Wang, Hong-Yan Liu, Yue-Hua Liu, Ke-Ru Qin, Jin-Rui Hu, Xin-Yang Li, Hong-Li Liu, Wei Wang, Zhao-Yang Chen, Chun-Fang Wang, Hai-Long Wang","doi":"10.14411/fp.2021.016","DOIUrl":null,"url":null,"abstract":"<p><p>The apicomplexan Toxoplasma gondii (Nicolle et Manceaux, 1908) secretes a group of serine/threonine kinases from rhoptries, which play vital roles in boosting intracellular infection. Toxoplasma gondii rhoptry organelle protein 17 (ROP17) is one of these important kinase proteins. Nevertheless, its function remains unclear. Here, we showed that ROP17 induced autophagy in vitro and in vivo. The autophagy of small intestine tissues of T. gondii tachyzoite (RH strain)-infected mice was detected by the immunohistochemistry staining of LC3B, Beclin 1 and P62. ROP17 overexpression augmented starvation-induced autophagy in HEK 293T cells as measured by MDC staining, transmission electron microscopy (TEM), fluorescence microscopy and Western blot analysis. Moreover, the interaction of ROP17 and Bcl-2 was confirmed using co-immunoprecipitation analysis, and the data demonstrated that ROP17 had an autophagic role dependent on the Beclin 1-Bcl-2 pathway, which was also revealed in an in vivo model through immunohistochemical staining. Pearson coefficient analysis showed that there existed strong positive correlations between the expression of ROP17 and LC3B, Beclin 1 and phosphorylation of Bcl-2, while strong negative correlations between the expression of ROP17 and p62 and Bcl-2. Collectively, our findings indicate that ROP17 plays a pivotal role in maintaining T. gondii proliferation in host cells via the promotion of autophagy-dependent survival.</p>","PeriodicalId":55154,"journal":{"name":"Folia Parasitologica","volume":"68 ","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2021-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Folia Parasitologica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.14411/fp.2021.016","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PARASITOLOGY","Score":null,"Total":0}
引用次数: 2
Abstract
The apicomplexan Toxoplasma gondii (Nicolle et Manceaux, 1908) secretes a group of serine/threonine kinases from rhoptries, which play vital roles in boosting intracellular infection. Toxoplasma gondii rhoptry organelle protein 17 (ROP17) is one of these important kinase proteins. Nevertheless, its function remains unclear. Here, we showed that ROP17 induced autophagy in vitro and in vivo. The autophagy of small intestine tissues of T. gondii tachyzoite (RH strain)-infected mice was detected by the immunohistochemistry staining of LC3B, Beclin 1 and P62. ROP17 overexpression augmented starvation-induced autophagy in HEK 293T cells as measured by MDC staining, transmission electron microscopy (TEM), fluorescence microscopy and Western blot analysis. Moreover, the interaction of ROP17 and Bcl-2 was confirmed using co-immunoprecipitation analysis, and the data demonstrated that ROP17 had an autophagic role dependent on the Beclin 1-Bcl-2 pathway, which was also revealed in an in vivo model through immunohistochemical staining. Pearson coefficient analysis showed that there existed strong positive correlations between the expression of ROP17 and LC3B, Beclin 1 and phosphorylation of Bcl-2, while strong negative correlations between the expression of ROP17 and p62 and Bcl-2. Collectively, our findings indicate that ROP17 plays a pivotal role in maintaining T. gondii proliferation in host cells via the promotion of autophagy-dependent survival.
期刊介绍:
FOLIA PARASITOLOGICA, issued in online versions, is an international journal that covers the whole field of general, systematic, ecological and experimental parasitology. It publishes original research papers, research notes and review articles. Contributions from all branches of animal parasitology, such as morphology, taxonomy, biology, biochemistry, physiology, immunology, molecular biology and evolution of parasites, and host-parasite relationships, are eligible. Novelty and importance in the international (not local or regional) context are required. New geographical records of parasites, records of new hosts, regional parasite and/or host surveys (if they constitute the principal substance of manuscript), local/regional prevalence surveys of diseases, local/regional studies on epidemiology of well known diseases and of parasite impact on human/animal health, case reports, routine clinical studies and testing of established diagnostic or treatment procedures, will not be considered. One species description will also not be considered unless they include more general information, such as new diagnostic characters, host-parasite associations, phylogenetic implications, etc. Manuscripts found suitable on submission will be reviewed by at least two reviewers.