title: Traumatic Brain Injury and Peripheral Immune Suppression: Primer and Prospectus.
abstract: Nosocomial infections are a common occurrence in patients following traumatic brain injury (TBI) and are associated with an increased risk of mortality, longer length of hospital stay, and poor neurological outcome. Systemic immune suppression arising as a direct result of injury to the central nervous system (CNS) is considered to be primarily responsible for this increased incidence of infection, a view strengthened by recent studies that have reported novel changes in the composition and function of the innate and adaptive arms of the immune system post-TBI. However, our knowledge of the mechanisms that underlie TBI-induced immune suppression is equivocal at best. Here, after summarizing our current understanding of the impact of TBI on peripheral immunity and discussing CNS-mediated regulation of immune function, we propose roles for a series of novel mechanisms in driving the immune suppression that is observed post-TBI. These mechanisms, which have never been considered before in the context of TBI-induced immune paresis, include the CNS-driven emergence into the circulation of myeloid-derived suppressor cells and suppressive neutrophil subsets, and the release from injured tissue of nuclear and mitochondria-derived damage associated molecular patterns. Moreover, in an effort to further our understanding of the mechanisms that underlie TBI-induced changes in immunity, we pose throughout the review a series of questions, which if answered would address a number of key issues, such as establishing whether manipulating peripheral immune function has potential as a future therapeutic strategy by which to treat and/or prevent infections in the hospitalized TBI patient.
authors.affiliation: NIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham , Birmingham , UK ; Institute of Inflammation and Ageing, University of Birmingham , Birmingham , UK.
authors.forename: Jon
authors.initials: J
authors.lastname: Hazeldine
authors.affiliation: NIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham , Birmingham , UK ; Institute of Inflammation and Ageing, University of Birmingham , Birmingham , UK.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Lord
authors.affiliation: NIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham , Birmingham , UK ; Institute of Inflammation and Ageing, University of Birmingham , Birmingham , UK.
authors.forename: Antonio
authors.initials: A
authors.lastname: Belli
keywords: immune suppression; immune system; infection; traumatic brain injury