The influence of autophagy on mouse inflammatory responses caused by Salmonella enterica serovar Typhimurium with spv genes
The influence of autophagy on mouse inflammatory responses caused by Salmonella enterica serovar Typhimurium with spv genes作者机构:Department of Medical Microbiology Medical School of Soochow University Suzhou 215123 China
出 版 物:《微生物与感染》 (Journal of Microbes and Infections)
年 卷 期:2011年第6卷第4期
页 面:205-213页
学科分类:0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术]
基 金:sponsored by Natural Science Foundation of China(No.30972768) Special Research Fund for the Doctoral Program of High Education(No.20103201110009) Natural Science Foundation of Jiangsu Province(No.BK2011286) Qinglan Project of Jiangsu Province(No.SR13400211)
摘 要:An investigation into the effects of Salmonella plasmid virulence genes (spv) on autophagy, apoptosis, and inflammation was carried out in mice, using a strain of Salmonella enterica serovar Typhimurium (S. typhimurium) SR-11 carrying spv. Strain BRD509 without spv was used as a control. Results showed that the expression of autophagy protein Beclin-1 in the livers and spleens in the SR-11 group was lower than that in the BRD509 group, while the apoptosis protein, Caspase-3, was higher in the SR-11 group. Inflammatory cytokine levels [interleukin 12 (IL-12) and interferon γ (IFN-γ)] were higher in the SR-11 group compared with those in the BRD509 group since 4 d post-infection. In addition, we found an increase in severe pathological changes and larger viable bacterial amounts in livers and spleens in the SR-11 group. After intervention with autophagy agonist rapamycin (RAPA), Beclin-1 expression increased in both groups, while Caspase-3 expression was different between the two groups: Caspase-3 decreased in the SR-11 group but increased in the BRD509 group. Moreover, RAPA decreased cytokine levels, bacterial quantity and organ-related injury in the SR-11 group whereas RAPA increased cytokine levels and aggravated organ injury in the BRD509 group. Results from these studies suggest that S. typhimurium with spv genes may exacerbate infection by inhibiting autophagy and affecting the production of inflammatory cytokines. RAPA-enhanced autophagy may improve the secretion of cytokines in order to protect the host from damaging by Salmonella infection. Our study suggests that the regulation of cellular autophagy may play a role in the prevention and control of certain infectious diseases.