Abstract
BackgroundSpinal cord injury (SCI) disrupts essential neuroimmune communication, leading to severe immune depression. Previous studies confirmed immune dysfunction in mice with chronic SCI and following high thoracic level injury where sympathetic innervation of the spleen is disrupted. Here, we induced a mid-thoracic injury where integrity of the sympathetic response is maintained and investigated the antiviral T cell response to influenza virus after acute SCI.MethodsOne week following a contusion SCI at thoracic level T9, mice were infected intranasally with influenza virus. Profiles of immune cell populations were analyzed before infection, and virus-specific CD8 T cell response was analyzed 7 days post-infection.ResultsFollowing intranasal infection, injured mice had prolonged recovery and significant weight loss. Importantly, expansion and effector functions of virus-specific CD8 T cells were decreased in injured mice. The compromised CD8 T cell response was associated with inflammation and stress responses initiated after injury. Regulatory mechanisms, including increased regulatory T cells (Tregs) and upregulated PD-1/PD-L1, were induced following SCI. Furthermore, we show that increased corticosterone (CORT) levels can inhibit CD8 T cells and that blocking CORT in vivo following SCI enhances CD8 T cell antiviral responses.ConclusionsOur results show that mice with mid-thoracic SCI have impaired CD8 T cell function during the acute stage of injury, indicating that impaired antiviral responses occur rapidly following SCI and is not dependent on injury level.
Highlights
Spinal cord injury (SCI) disrupts essential neuroimmune communication, leading to severe immune depression
Studies were performed to determine if the CD8 T cell response to influenza infection is impaired at an acute stage following SCI
One third of the SCI mice were removed from the study because of severe body weight loss (> 25% initial BW) after the infection, and all of the uninjured mice survived the challenge
Summary
Spinal cord injury (SCI) disrupts essential neuroimmune communication, leading to severe immune depression. In addition to impaired motor function, SCI leads to multiple organ dysfunction and complications and increased susceptibility to pathogen infection [2]. SCI and other disorders of the nervous system are known to induce severe immune depression resulting in increased risk of infections [1, 3,4,5]. Emergence of pandemic flu strains in the past decade have heightened the awareness that immune-compromised patients, such as those suffering from SCI, are more susceptible to a new strain of influenza virus [7]. Reducing complications from respiratory infections and understanding the mechanisms contributing to immune dysfunction are critical for improving the health and life span of SCI patients
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