Immunological and Clinical Monitoring of Patients With Septic Shock in Intensive Care Unit : In-depth Immunophenotyping of Circulating Immunoregulatory Cells During Sepsis

Septic syndromes are a major although largely under-recognized health care problem and represent the first cause of mortality in intensive care units (ICU). While it has long been known that sepsis deeply perturbs immune homeostasis by inducing a tremendous systemic inflammatory response, novel findings indicate that sepsis indeed initiates a more complex immune response that varies over time, with the concomitant occurrence of both pro- and anti-inflammatory mechanisms. As a resultant, after a short pro-inflammatory phase, septic patients enter a stage of protracted immunosuppression. This is illustrated in those patients by reactivation of dormant viruses (cytomegalovirus (CMV) or Herpes Simplex Virus (HSV)) or infections due to pathogens, including fungi, which are normally pathogenic solely in immunocompromised hosts. These alterations might be directly responsible for worsening outcome in patients who survived initial resuscitation as nearly all immune functions are deeply compromised. New promising therapeutic strategies are currently emerging from those recent findings such as adjunctive immunostimulation for the most immunosuppressed patients.

Recent studies have described the induction of immunoregulatory cells (of myeloid and lymphoid origin) following septic shock and have revealed a similar induction kinetics across all subpopulations of regulatory cells. Nevertheless, these observations need to be confirmed and linked to the underlying mechanisms responsible for the induction of these cells (notably the activation of the inflammasome pathway), which remain largely unknown.

IMMUNOSEPSIS 5 study will therefore, as part of a prospective observational study involving a large cohort of patients, demonstrate the concurrent induction of all regulatory cell subpopulations following sepsis and the activation of the hyper-inflammatory response, including the inflammasome pathway. The association between these parameters and patient outcomes will also be assessed (death and/or the occurrence of a secondary infection).