结核分枝杆菌
自噬
肺结核
生物
免疫学
肺
脾脏
牛分枝杆菌
卡介苗
接种疫苗
医学
微生物学
病理
细胞凋亡
内科学
生物化学
作者
Michel de Jesús Aceves-Sánchez,Jorge Barrios‐Payan,Cristian Alfredo Segura-Cerda,Mario Alberto Flores-Valdéz,Dulce Mata-Espinosa,César Pedroza-Roldán,Rahul Yadav,Deepak Kumar Saini,Miguel Angel de la Cruz,Miguel A. Ares,Helle Bielefeldt‐Ohmann,Guillermina Baay-Guzmán,Isabelle Vergne,Jesús Bernardino Velázquez-Fernández,Jeannette Barba León,Rogelio Hernández-Pando
出处
期刊:Vaccine
[Elsevier]
日期:2023-06-01
卷期号:41 (26): 3824-3835
被引量:1
标识
DOI:10.1016/j.vaccine.2023.04.065
摘要
The efficacy of BCG vaccines against Mycobacterium tuberculosis (Mtb) strains of lineage 2 (Beijing) in preclinical models and humans has been questioned. We have developed BCG∆BCG1419c, by deletion of BCG1419c in BCG Pasteur, which improved control of tuberculosis (TB) in preclinical models. Here, we compared the capacity of BCG and BCG∆BCG1419c to induce autophagy in murine macrophages, modify c-di-GMP content and transcript levels of BCG1416c, encoding the enzyme responsible for c-di-GMP synthesis/degradation, and of BCG1419c, encoding the phosphodiesterase involved in c-di-GMP degradation. Furthermore, we evaluated proteomic differences in vitro and compared protection against TB produced by a low dose of the HN878-Beijing strain at 3- and 6-months post-infection. We found that BCG∆BCG1419c induced more autophagy and produced different levels of c-di-GMP as well as different transcription of BCG1416c with no expression of BCG1419c. BCG∆BCG1419c differentially produced several proteins, including some involved in interaction with host cells. Vaccination with either BCG strain led to control of bacillary burden in lungs and spleen at 3- but not 6-months post-infection, whereas it reduced pneumonic areas compared with unvaccinated controls at 6 months post-infection. Vaccination with BCG∆BCG1419c delayed progression of lung necrosis as this was observed only at 6 months post-infection. Taken together, compared with BCG, BCG∆BCG1419c increased autophagy, presented different levels of c-di-GMP and transcription of BCG1416c in vitro in a growth-phase dependent manner, modified its proteome and delayed progression of lung pathology produced by a highly virulent Beijing strain.
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