title: Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level.
abstract: Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P < 0.001) independently from mechanical ventilation and preserved sensory function by multiple regression analysis. We present evidence that spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner.
authors.affiliation: 1 Department of Neurology and Experimental Neurology, Spinal Cord Injury Research (Molecular Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Germany 1 Department of Neurology and Experimental Neurology, Spinal Cord Injury Research (Molecular Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Brommer
authors.affiliation: 3 Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Odilo
authors.initials: O
authors.lastname: Engel
authors.affiliation: 1 Department of Neurology and Experimental Neurology, Spinal Cord Injury Research (Molecular Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Kopp
authors.affiliation: 1 Department of Neurology and Experimental Neurology, Spinal Cord Injury Research (Molecular Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Watzlawick
authors.affiliation: 3 Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Müller
authors.affiliation: 1 Department of Neurology and Experimental Neurology, Spinal Cord Injury Research (Molecular Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Germany 4 German Centre for Neurodegenerative Diseases (DZNE), Berlin, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Prüss
authors.affiliation: 5 National Spinal Cord Injury Statistical Centre, Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 5 National Spinal Cord Injury Statistical Centre, Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: DeVivo
authors.affiliation: 1 Department of Neurology and Experimental Neurology, Spinal Cord Injury Research (Molecular Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Felix W
authors.initials: FW
authors.lastname: Finkenstaedt
authors.affiliation: 3 Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Germany 4 German Centre for Neurodegenerative Diseases (DZNE), Berlin, Germany 6 Cluster of Excellence NeuroCure, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
authors.affiliation: 7 Centre for Spinal Cord Injury, Trauma Hospital Berlin, Warener Straße 7, 12683 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Liebscher
authors.affiliation: 3 Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Germany 6 Cluster of Excellence NeuroCure, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meisel
authors.affiliation: 1 Department of Neurology and Experimental Neurology, Spinal Cord Injury Research (Molecular Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Germany 8 Department of Neurology, Spinal Cord Injury Division, The Neurological Institute, The Ohio State University, Wexner Medical Centre, Columbus, OH 43210, USA 9 Department of Neuroscience and Centre for Brain and Spinal Cord Repair, Department of Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Centre, Columbus, OH 43210, USA Jan.Schwab@osumc.edu.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Schwab
mesh_terms: D000818:Animals; D004198:Disease Susceptibility; D007153:Immunologic Deficiency Syndromes / Q000209:etiology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013119:Spinal Cord Injuries / Q000150:complications* / Q000473:pathology*; D013904:Thoracic Vertebrae / Q000293:injuries* / Q000473:pathology*
keywords: mechanisms; myelopathy; neuroinflammation; rehabilitation; spinal cord injury