Chronic spinal cord injury attenuates influenza virus-specific antiviral immunity

Valerie Bracchi-Ricard, Ji Zha, Annalise Smith, Darlah M. Lopez-Rodriguez, John R. Bethea, Samita Andreansky

Individuals suffering from spinal cord injury (SCI) are at higher risk for respiratory-related viral infections such as influenza. In a previous study (Zha et al., J Neuroinflammation 11:65, 2014), we demonstrated that chronic spinal cord injury caused impairment in CD8(+)T cell function with increased expression of the immunosuppressive protein, programmed cell death 1 (PD-1). The present study was undertaken to establish whether chronic SCI-induced immune deficits would affect antiviral immunity directed against primary and secondary infections. Six to seven weeks following a SCI contusion at thoracic level T9, mice were infected intranasally with influenza virus. Virus-specific immunity was analyzed at various time points post-infection and compared to uninjured controls. We report that chronic thoracic SCI impairs the ability of the animals to mount an adequate antiviral immune response. While all uninjured control mice cleared the virus from their lungs by day 10 post-infection, a significant number (approximately 70 %) of chronic SCI mice did not clear the virus and succumbed to infection-induced mortality. This was attributed to severe deficits in both virus-specific antibody production and CD8(+) T cell response in injured mice after primary infection. We also determined that previously acquired humoral immunity was maintained after spinal cord injury as vaccination against influenza A prior to injury-protected mice from a homologous viral challenge. In contrast, prior immunization did not protect mice from a heterotypic challenge with a different strain of influenza virus. Taken together, our data demonstrate that chronic SCI attenuates virus-specific humoral and cellular immunity during the establishment of primary response and impairs the development of memory CD8(+) T cells. In contrast, B cell memory acquired through vaccination prior to SCI is preserved after injury which demonstrates that antigen-specific memory cells are refractory following injury. Our study defines important parameters of the deficits of chronic SCI-induced immune depression during a viral respiratory infection. Our objective is to better understand the mechanisms of spinal cord injury-induced immune depression with the goal of developing more effective therapies and reduce mortality due to complications from influenza and other infections.