The therapeutic potential of epigenetic manipulation during infectious diseases

Pharmacol Ther. 2016 Nov;167:85-99. doi: 10.1016/j.pharmthera.2016.07.013. Epub 2016 Aug 9.

Abstract

Epigenetic modifications are increasingly recognized as playing an important role in the pathogenesis of infectious diseases. They represent a critical mechanism regulating transcriptional profiles in the immune system that contributes to the cell-type and stimulus specificity of the transcriptional response. Recent data highlight how epigenetic changes impact macrophage functional responses and polarization, influencing the innate immune system through macrophage tolerance and training. In this review we will explore how post-translational modifications of histone tails influence immune function to specific infectious diseases. We will describe how these may influence outcome, highlighting examples derived from responses to acute bacterial pathogens, models of sepsis, maintenance of viral latency and HIV infection. We will discuss how emerging classes of pharmacological agents, developed for use in oncology and other settings, have been applied to models of infectious diseases and their potential to modulate key aspects of the immune response to bacterial infection and HIV therapy.

Keywords: Chromatin; Epigenetic; Immune regulation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-HIV Agents / pharmacology
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / genetics
  • Bacterial Infections / immunology
  • Drug Design
  • Epigenesis, Genetic*
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / immunology
  • Histones / metabolism
  • Humans
  • Immunity, Innate
  • Macrophages / metabolism
  • Sepsis / drug therapy
  • Sepsis / genetics
  • Sepsis / immunology

Substances

  • Anti-Bacterial Agents
  • Anti-HIV Agents
  • Histones