摘要
The intracellular pathogen Mycobacterium tuberculosis(Mtb)can survive in the host and cause disease by interfering with a variety of cellular functions.The mammalian cell entry 2(mce2)operon of Mtb has been shown to contribute to tuberculosis pathogenicity.However,little is known about the regulatory roles of Mtb Mce2 family proteins towards host cellular functions.Here we show that the Mce2 family protein Mce2E suppressed the macrophage innate immune response and promoted epithelial cell proliferation.Mce2E inhibited activation of the extracellular signal-regulated kinase(ERK)and Jun N-terminal kinase(JNK)mitogen-activated protein kinase(MAPK)signaling pathways in a non-canonical D motif(a MAPK-docking motif)-dependent manner,leading to reduced expression of TNF and IL-6 in macrophages.Furthermore,Mce2E promoted proliferation of human lung epithelium-derived lung adenoma A549 cells by inhibiting K48-linked polyubiquitination of eEF1A1 in aβstrand region-dependent manner.In summary,Mce2E is a novel multifunctional Mtb virulence factor that regulates host cellular functions in a niche-dependent manner.Our data suggest a potential novel target for TB therapy.
基金
This work was supported by research funding from the National Key Research and Development Program of China(Grant Nos.2017YFA0505900 and 2017YFD0500300)
the National Basic Research Programs of China(Grant No.2014CB74440)
the National Natural Science Foundation of China(Grant Nos.81571536 and 81571954)
the Beijing Natural Science Foundation(Grant No.5162021)
the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDPB03)
the Youth Innovation Promotion Association CAS.
