Rao Shanshan, Xu Tao, Xia Yu, Zhang Hongfeng
Department of Pathology, Wuhan Central Hospital, Huazhong University of Science and Technology, Wuhan, China.
Cancer Biology Research Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Front Microbiol. 2020 Nov 26;11:573844. doi: 10.3389/fmicb.2020.573844. eCollection 2020.
Phagosome- and xenophagosome-lysosome systems play a critical role in the defense of pathogenic bacteria, such as and , in macrophages. A great part of the bacteria escapes from the digestion and can survive through some mechanisms that are still poorly understood and which require further exploration. Here we identified that inhibited the expression and activation of TFEB to blunt the functions of lysosomes and defense of clearance by activating caspase-1. The expression and activation of TFEB were enhanced early under the infection of , which was followed by shrinkage to weaken lysosomal functions due to the delayed activation of ERK, mTOR, and STAT3. Thus, we have identified novel escape mechanisms for and to deepen and strengthen our strategies fighting with pathogens.
吞噬体和异噬性吞噬体-溶酶体系统在巨噬细胞抵御诸如[具体细菌名称未给出]等病原菌的过程中发挥着关键作用。很大一部分细菌能够逃避消化,并可通过一些仍未被充分了解且有待进一步探索的机制存活下来。在此,我们发现[具体物质未给出]通过激活半胱天冬酶-1来抑制转录因子EB(TFEB)的表达和激活,从而削弱溶酶体的功能以及清除防御能力。在[具体细菌名称未给出]感染早期,TFEB的表达和激活增强,但随后由于细胞外信号调节激酶(ERK)、哺乳动物雷帕霉素靶蛋白(mTOR)和信号转导子和转录激活子3(STAT3)的延迟激活,TFEB表达和激活出现减少,进而导致溶酶体功能减弱。因此,我们确定了[具体细菌名称未给出]新的逃逸机制,以深化和加强我们对抗病原体的策略。