[Role and application of programmed death protein 1 (PD-1) and its ligand PD-L1 in immune cell dysfunction in sepsis:...

Immunosuppression is increasingly being recognized as one of the causes of increased morbidity and mortality during sepsis. Both innate and adaptive immune system dysfunction have been shown to cause an impaired ability to eradicate the primary infection and also lead to frequent occurrence of secondary opportunistic infections. Immune checkpoint molecules, such as programmed death 1 (PD-1) and PD-1 ligand 1 (PD-L1), are up-regulated during the immunosuppressive phase of sepsis, not only on adaptive immune cells (such as T cells), but also on innate immune cells (such as macrophages, monocytes, neutrophils) as well as non-immune cells, resulting in functional changes, often with adverse sequelae. In numerous pre-clinical models of sepsis, therapeutic agents for blocking engagement of inhibitory immune checkpoints on immune cells have been shown to improve innate and adaptive immune cell functions, increase host resistance to infection and significantly improve survival.