Injury, sepsis, and the regulation of Toll-like receptor responses

Abstract: Although we tend to think that the immune system has evolved to protect the host from invading pathogens and to discriminate be-tween self and nonself, there must also be an ele-ment of the immune system that has evolved to control the response to tissue injury. Moreover, these potential immune-regulatory pathways con-trolling the injury response have likely coevolved in concert with self and nonself discriminatory im-mune-regulatory networks with a similar level of complexity. From a clinical perspective, severe injury upsets normal immune function and can pre-dispose the injured patient to developing life-threatening infectious complications. This remains a significant health care problem that has driven decades of basic and clinical research aimed at defining the functional effects of injury on the im-mune system. This review and update on our on-going research efforts addressing the immunologi-cal response to injury will highlight some of the most recent advances in our understanding of the impact that severe injury has on the innate and adaptive immune system focusing on phenotypic changes in innate immune cell responses to Toll-like receptor stimulation. J. Leukoc. Biol. 75