Neutrophil heterogeneity and its role in infectious complications after severe trauma

Abstract

Background: Trauma leads to a complex inflammatory cascade that induces both immune activation and a refractory immune state in parallel. Although both components are deemed necessary for recovery, the balance is tight and easily lost. Losing the balance can lead to life-threatening infectious complications as well as long-term immunosuppression with recurrent infections. Neutrophils are known to play a key role in these processes. Therefore, this review focuses on neutrophil characteristics and function after trauma and how these features can be used to identify trauma patients at risk for infectious complications.

Results: Distinct neutrophil subtypes exist that play their own role in the recovery and/or development of infectious complications after trauma. Furthermore, the refractory immune state is related to the risk of infectious complications. These findings change the initial concepts of the immune response after trauma and give rise to new biomarkers for monitoring and predicting inflammatory complications in severely injured patients.

Conclusion: For early recognition of patients at risk, the immune system should be monitored. Several neutrophil biomarkers show promising results and analysis of these markers has become accessible to such extent that they can be used for point-of-care decision making after trauma.

Keywords: Immune response; Infection; Neutrophil; Trauma.

Fig. 1

Concept of inflammatory response after trauma. Trauma leads to a rapid immune activation, during which the most competent neutrophils are mobilized into tissues, leaving supposedly less competent neutrophils behind in the circulation. The green lines represent the uncomplicated course after trauma. The immune response can become dysregulated by overwhelming immune activation (upper red line), a refractory immune state (lower red line) or low-grade inflammation and immune impairment later on (both red lines). The vertical axis indicates the immune status. The horizontal axis represents time after trauma. SIRS systemic inflammatory response syndrome, PICS persistent inflammation, immunosuppression, and catabolism syndrome

Fig. 2

Schematic representation of theories regarding neutrophil subtypes and post-traumatic inflammatory complications. Under homeostatic conditions, there is a homogeneous population of mature neutrophils circulating in the peripheral blood. After trauma, large amounts of immature banded neutrophils enter the circulation. Injury leads to activation of neutrophils and the most activated neutrophils migrate into tissues, leaving less responsive and possibly less competent neutrophils behind in the circulation (the refractory neutrophils). Hypersegmented neutrophils are released into the blood stream after several days post-injury. These cells are known for their decreased bacterial killing after adequate phagocytosis. Therefore, these cells could function as Trojan horses contributing to blood stream infections, especially when present in combination with refractory neutrophils. Also, granulocytic MDSCs with immunosuppressive and immunostimulatory properties are observed after trauma. Persistent expansion of this granulocytic MDSC pool is associated with recurrent infection, prolonged ICU stay, and increased mortality, consistent with the PICS phenotype. MDSC myeloid derived suppressor cells, ICU intensive care unit, PICS persistent inflammation, immunosuppression, and catabolism syndrome