Immune response to traumatic injury: harmony and discordance of immune system homeostasis

Trauma remains one of the leading causes of death worldwide. Traumatic injury disrupts immune system homeostasis and may predispose patients to opportunistic infections and inflammatory complications. Prevention of multiple organ dysfunction syndrome due to septic complications following severe trauma is a challenging problem. Following severe injury, the immune system usually tends toward a pro-inflammatory phenotype and then changes to a counter-inflammatory phenotype. This immune system homeostasis is believed to be a protective response based on the balance between the innate and adaptive immune systems. We reported that injury activates inflammasomes and primes Toll-like receptors. The primed innate immune system is prepared for a rapid and strong antimicrobial immune defense. However, trauma can also develop the two-hit response phenotype. We also reported that injury augments regulatory T cell activity, which can control the two-hit response phenotype in trauma. We discuss the current idea that traumatic injury induces a unique type of innate and adaptive immune response that may be triggered by damage-associated molecular pattern molecules, which are a combination of endogenous danger signal molecules that include alarmins and pathogen-associated molecular pattern molecules.