Persistent activation of TNFR1 on spinal cord interneurons contributes to immune dysfunction after spinal cord injury in rodents

Abstract Spinal cord injury (SCI) is a devastating condition with 250,000 to 500,000 new cases globally each year. Respiratory infections, e.g., pneumonia and influenza, are the leading cause of death after SCI. For instance, an individual SCI 37 times more likely become infected hospitalized from flu. Yet, field has poor understanding how immune dysfunction arises trauma central nervous system (CNS) altered neuro-immune communication impacts individual’s outcome infection. In humans rodents, leads maladaptive changes in spinal-sympathetic reflex (SSR) circuit which crucial sympathetic function. Soluble Tumor Necrosis Factor (sTNF) pro-inflammatory cytokine that elevated CNS remains for several months injury. We recently demonstrated blocking TNFR1 activation CNS, using XPro1595, decreased excitability SpINs SSR improved response infection hypothesize hyper-excitability glutamatergic due persistent contributes dysfunction. To test this, we utilized viral mediated targeted knock-down on excitatory SpINs, inhibiting interneurons function, including increase virus-specific T cells decrease load remaining lung Supported by grants NIH (R01 NS111761)