Epigenetics As The Driving Force In Long-Term Immunosuppression

Jose Luis Garcia Gimenez,Nieves Edurne Carbonell

doi:10.21767/2472-1158.100017

Abstract

Epigenetics is an emerging frontier of biology, with the potential for deciphering the intricate molecular and transcriptional cellular programs, therefore contributing to explain the pathological evolution of sepsis, one of the most elusive syndromes in medicine. The evolution of sepsis depends not only on the pathogen which originated the infection but also on the genetic and epigenetic background of the host. Short-term mortality of sepsis and septic shock is high, being considered a public health concern worldwide. Immunosuppression is the predominant driving force for morbidity and mortality in late deaths and long-term deaths of survivors from a sepsis episode. In this regard, apoptosis of immune cells and complex epigenetic reprogramming in immune and progenitor cells may contribute to the immunoparalysis observed in post-septic patients, who are prone to the apparition of new, opportunistic infections. Here, we review the literature and expose the most relevant results which explain the epigenetic programs contributing to the progression of sepsis. Furthermore, we revisit the role of circulating histones in the pathogenesis of sepsis and septic shock and finally we discuss about the therapeutic potential of epigenetic drugs in the treatment of sepsis.

Highlights

Corresponding author: Jose Luis Garcia GimenezSepsis is defined as the host inflammatory response to severe, life-threatening infection, with the presence of biochemical abnormalities and organ dysfunction
Both phases occur steeply throughout the progression of sepsis, with the early phase of sepsis evolving with an important participation of pro-inflammatory pathways, and the latter phase of sepsis characterized by immunosuppression, which conduces to development of secondary infections or virus reactivation, increasing the probability of late-deaths
Epigenetic mechanisms are the conductors of specific chromatin signatures and transcriptional programs in immune cells, conditioning the pro-inflammatory and anti-inflammatory responses in septic patients

Summary

Introduction

Corresponding author: Jose Luis Garcia GimenezSepsis is defined as the host inflammatory response to severe, life-threatening infection, with the presence of biochemical abnormalities and organ dysfunction. Among others, circulating histones mediate the apoptosis of these immune cells, compromising the immune defenses and contributing to immunosuppression after septic shock, producing late deaths.

Results

Conclusion