Regulatory T Cells: Angels or Demons in the Pathophysiology of Sepsis?

Abstract

Sepsis is a syndrome characterized by life-threatening organ dysfunction caused by the dysregulated host response to an infection. Sepsis, especially septic shock and multiple organ dysfunction is a medical emergency associated with high morbidity, high mortality, and prolonged after-effects. Over the past 20 years, regulatory T cells (Tregs) have been a key topic of focus in all stages of sepsis research. Tregs play a controversial role in sepsis based on their heterogeneous characteristics, complex organ/tissue-specific patterns in the host, the multi-dimensional heterogeneous syndrome of sepsis, the different types of pathogenic microbiology, and even different types of laboratory research models and clinical research methods. In the context of sepsis, Tregs may be considered both angels and demons. We propose that the symptoms and signs of sepsis can be attenuated by regulating Tregs. This review summarizes the controversial roles and Treg checkpoints in sepsis.

Keywords: checkpoints; pathophysiology; regulatory T cells; secondary infections; sepsis.

Figure 1

Factors that lead to the controversy surrounding the role of regulatory T cells in sepsis.

Figure 2

The antagonism between the host and pathogenic microorganisms. The spread of pathogens, especially Gram-negative bacteria, and their products [such as lipopolysaccharide (LPS), etc.] causes systemic inflammatory response syndrome (SIRS), which leads to multiple organ dysfunction syndromes (MODS) and shock, and even death. However, surviving patients suffer from a stage of compensatory anti-inflammatory response syndrome (CARS), especially immunosuppression, and experience a long-term immune dysfunction called immuno-paralysis. And they are more susceptible to secondary infections, increased viral activation, and reduced 5-year survival rate, compared to those who do not have sepsis.