title: Mycobacterium tuberculosis EIS gene inhibits macrophage autophagy through up-regulation of IL-10 by increasing the acetylation of histone H3.
abstract: Autophagy plays a crucial role in the progress of Mycobacterium tuberculosis (MTB) infection. Recently, MTB enhanced intracellular survival (EIS) protein was reported to be secreted from MTB cells and linked to the inhibition of autophagy and the intracellular persistence of the pathogen. Here, we investigated the mechanism of EIS-mediated inhibition of autophagy in a human phorbol myristate acetate (PMA)-treated THP-1 cell line as well as in murine macrophages. We confirmed that the presence of EIS led to the inhibition of rapamycin (Rapa)-induced autophagy, while IL-10 gene expression was increased and Akt/mTOR/p70S6K pathway was activated during the process. IL-10 gene silencing led to a significant recovery of EIS-mediated autophagy suppression and decreased activity of the Akt/mTOR/p70S6K pathway. IL-10 promoter activity was unaffected by EIS. Remarkably, EIS increased the acetylation level of histone H3 (Ac-H3), which binds to the SP1 and STAT3 region of the human IL-10 gene promoter sequence. Thus, EIS protein possibly increased IL-10 expression through the regulation of Ac-H3 of its promoter. Our data demonstrated that one possible mechanism of the MTB evasion of autophagy is that the EIS protein up-regulates IL-10 via Ac-H3 and thus activates Akt/mTOR/p70S6K pathway.
authors.affiliation: Department of Laboratory Medicine, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Duan
authors.affiliation: Department of Respiratory, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yi
authors.affiliation: Department of Laboratory Medicine, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Respiratory, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400010, China. Electronic address: lsj1025@163.com.
authors.forename: Shengjin
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400010, China. Electronic address: chenweixian75@163.com.
authors.forename: Weixian
authors.initials: W
authors.lastname: Chen
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases; D000942:Antigens, Bacterial / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D008264:Macrophages / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000166:cytology / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006657:Histones; D016753:Interleukin-10; D000123:Acetyltransferases; C430563:Eis protein, Mycobacterium tuberculosis
keywords: Autophagy; Histone acetylation; Interleukin 10; Mycobacterium tuberculosis