trichostatin-a and Tuberculosis

The rapid and persistent increase of drug-resistant

Topics: Animals; Antitubercular Agents; Benzamides; Blood Donors; Cell Survival; Cells, Cultured; Cytokines; Disease Models, Animal; Histone Deacetylase Inhibitors; Histone Deacetylases; Host-Pathogen Interactions; Humans; Hydroxamic Acids; Macrophages; Mycobacterium marinum; Mycobacterium tuberculosis; Oxadiazoles; Signal Transduction; Transcriptome; Treatment Outcome; Tuberculosis; Zebrafish

Histone deacetylase inhibitors (HDACi), a novel class of anti-cancer drug, have been recently reported to suppress host immunity and increase susceptibility to infection. Tuberculosis, a leading infectious disease killer caused by Mycobacterium tuberculosis (M.tb), is basically the product of the interaction between bacterial virulence and host resistance. However, the effects of HDACi in host immunity against M.tb is largely unknown. In this study, we found that HDACi including Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) significantly impaired phagocytosis and killing activity of macrophage. In line with these findings, we noted that M.tb induced reactive oxygen species (ROS) production and autophagy are significantly suppressed by TSA. Transcriptome analysis revealed that the suppression of autophagy by TSA might due to its inhibiting autophagy-regulating genes such as CACNA2D3, which regulates intracellular Ca

Topics: Animals; Autophagy; Bacterial Load; Cells, Cultured; Colony Count, Microbial; Disease Susceptibility; Female; Gene Expression Regulation; Histone Deacetylase Inhibitors; Host Microbial Interactions; Humans; Hydroxamic Acids; Macrophages; Mice, Inbred C57BL; Mycobacterium tuberculosis; Phagocytosis; Reactive Oxygen Species; Tuberculosis; Vorinostat