Zhang Jiaoer, Sun Bin, Huang Ying, Kouadir Mohammed, Zhou Xiangmei, Wang Yang, Zhao Deming
State Key Lab of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
FEMS Immunol Med Microbiol. 2010 Dec;60(3):191-8. doi: 10.1111/j.1574-695X.2010.00732.x. Epub 2010 Sep 28.
Macrophage apoptosis represents an important innate defense mechanism against intracellular mycobacterial infection. Previous publications have shown that interferon-γ (IFN-γ) is involved in apoptosis of immune cells infected with mycobacteria. In this study, the impact of IFN-γ treatment on phorbol-12-myristate-13-acetate-differentiated THP-1 cells infected with Mycobacterium bovis was investigated. The results showed that IFN-γ increased apoptosis of THP-1 cells infected with M. bovis at a low multiplicity of infection (MOI) in a time-dependent manner. The percentage of cells undergoing apoptosis in IFN-γ-treated THP-1 cells increased from 4.3% at 12 h to 36.5% at 72 h upon infection with an MOI of 10. Activation of caspases-3 and -8 increased 8.3- and 6.7-fold, respectively. Neutralizing endogenous tumor necrosis factor-α (TNF-α) significantly inhibited IFN-γ-induced apoptosis of M. bovis-infected THP-1 cells. No significant change in IFN-γ-induced apoptosis was observed in M. bovis-infected cells after the addition of c-Jun N-terminal kinase and NF-κB pathways' inhibitors. Translocation of apoptosis-inducing factor (AIF) to the nucleus of M. bovis-infected THP-1 cells was observed in 23.4% of IFN-γ-treated cells, compared with 11.0% in untreated cells. Taken together, these results suggest that IFN-γ promotes apoptosis of M. bovis-infected THP-1 cells during early infection through the TNF-α-mediated death receptor and the AIF apoptotic pathway.
巨噬细胞凋亡是针对细胞内分枝杆菌感染的一种重要天然防御机制。先前的出版物表明，干扰素-γ（IFN-γ）参与感染分枝杆菌的免疫细胞的凋亡。在本研究中，研究了IFN-γ处理对感染牛分枝杆菌的佛波醇-12-肉豆蔻酸酯-13-乙酸酯分化的THP-1细胞的影响。结果表明，在低感染复数（MOI）时，IFN-γ以时间依赖性方式增加感染牛分枝杆菌的THP-1细胞的凋亡。在用MOI为10感染后，IFN-γ处理的THP-1细胞中发生凋亡的细胞百分比从12小时时的4.3%增加到72小时时的36.5%。半胱天冬酶-3和-8的激活分别增加了8.3倍和6.7倍。中和内源性肿瘤坏死因子-α（TNF-α）显著抑制IFN-γ诱导的感染牛分枝杆菌的THP-1细胞的凋亡。在添加c-Jun N端激酶和NF-κB途径抑制剂后，在感染牛分枝杆菌的细胞中未观察到IFN-γ诱导的凋亡有显著变化。在23.4%的IFN-γ处理细胞中观察到凋亡诱导因子（AIF）易位至感染牛分枝杆菌的THP-1细胞的细胞核，而未处理细胞中的这一比例为11.0%。综上所述，这些结果表明，IFN-γ在早期感染期间通过TNF-α介导的死亡受体和AIF凋亡途径促进感染牛分枝杆菌的THP-1细胞的凋亡。
