Mycobacterium tuberculosis infection induces IL-10 gene expression by disturbing histone deacetylase 6 and histonedeacetylase 11 equilibrium in macrophages

Abstract

Mycobacterium tuberculosis (MTB) infection is a significant contributor to dysregulated T cell-mediated immune response. Here we aimed to evaluate the mechanism of MTB infection in promoting interleukin-10 (IL-10) upregulation. The IL-10 levels in MTB infected THP-1 cells were evaluated with enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR). In challenged THP-1 cells, the HDAC6 and HDAC11 mRNA and protein levels were monitored at varied duration after MTB infection. Further, chromatin immunoprecipitation (ChIP) analysis was used to investigate the interaction between IL-10 expression and HDAC6 or HDAC11. HDAC6 and HDAC11 were overexpressed or silenced to study their effects on IL-10 regulation. IL-10 was upregulated after MTB challenge in a time- and dose-dependent manner. Similarly, HDAC6 and HDAC11 were also upregulated by MTB challenge. Overexpression or silencing of HDAC6 and HDAC11 changed IL-10 expression correspondingly. MTB infection disturbs the HDAC6/HDAC11 levels to induce IL-10 expression. Strategies to counteract the dysregulation of HDAC6/HDAC11 would potentially alleviate the immunological disordered following MTB infection.