MTOR involved in bacterial elimination against Trueperella pyogenes infection based on mice model by transcriptome and biochemical analysis

摘要

Trueperella pyogenes is an importantly opportunistic and commensal pathogen that causes suppurative lesions of most economically important livestock. To understand the molecular mechanism underlying the infection by T. pyogenes, we carried out a large-scale transcriptome sequencing of mice livers intraperitoneally infected with T. pyogenes using RNA-sequencing. A total of 47 G clean bases were obtained and 136 differentially expressed genes were detected between the control and the infection groups in the liver transcriptomes. Additionally, we found that the expression of a key autophagy regulator, mTOR (mechanistic target of rapamycin) was significantly upregulated in the infection groups. Mechanistically, T. pyogenes infection induced the expression of mTOR and subsequently inhibited the autophagy of host cell. Blocking autophagy with inhibitor 3-methyladenine (3-MA) or silencing autophagy-related gene 7 (Atg7) reduced the effect of bacterial elimination. Interestingly, inhibition of mTOR induced autophagy and reduced T. pyogenes viability in RAW264.7 murine macrophages. The silencing mTOR regulated oxidation and cytokines (interleukin-1 beta, IL-6 and tumor necrosis factro-alpha) against T. pyogenes in macrophages and significantly protected mice from T. pyogenes challenge. These findings indicate that mTOR is a novel functional regulator in autophagy-mediated T. pyogenes elimination and will be useful to further knowledge on the development of effective therapeutic strategy to control T. pyogenes-related diseases.