Tuberculosis caused by Mycobacterium tuberculosis remains a serious global public health threat. M. tuberculosis PE and PPE proteins are closely involved in pathogen-host interaction. To explore the predicted function of the M. tuberculosis PE17 (Rv1646), we heterologously expressed PE17 in a non-pathogenic Mycobacterium smegmatis strain (Ms_PE17). PE17 can reduce the survival of M. smegmatis within macrophages associated with altering the transcription levels of inflammatory cytokines IL1β, IL6, TNFα, and IL10 in Ms_PE17 infected macrophages through JNK signaling. Furthermore, macrophages apoptosis was increased upon Ms_PE17 infection in a caspases-dependent manner, accompanied by the activation of the Endoplasmic Reticulum stress IRE1α/ASK1/JNK signaling pathway. This can be largely interpreted by the epigenetic changes through reduced H3K9me3 chromatin occupancy post Ms_PE17 infection. To our knowledge, this is the first report that PE17 altered the macrophages apoptosis via H3K9me3 mediated chromatin remodeling.

由结核分枝杆菌引起的结核病仍然是严重的全球公共卫生威胁。结核分枝杆菌PE 和 PPE 蛋白密切参与病原体-宿主相互作用。为了探索结核分枝杆菌PE17 (Rv1646)的预测功能，我们在非致病性耻垢分枝杆菌菌株 (Ms_PE17) 中异源表达 PE17 。PE17可以降低耻垢分枝杆菌的存活率在巨噬细胞内，与通过 JNK 信号传导改变 Ms_PE17 感染的巨噬细胞中炎性细胞因子 IL1β、IL6、TNFα 和 IL10 的转录水平相关。此外，Ms_PE17 感染后巨噬细胞凋亡以半胱天冬酶依赖性方式增加，伴随着内质网应激 IRE1α/ASK1/JNK 信号通路的激活。这在很大程度上可以通过 Ms_PE17 感染后 H3K9me3 染色质占有率降低导致的表观遗传变化来解释。据我们所知，这是首次报道 PE17 通过 H3K9me3 介导的染色质重塑改变巨噬细胞凋亡。