RIG-LIKE receptor signaling modulates the innate immune response and astrocyte activation after injury to the spinal cord (157.6)

Abstract

Abstract Injury to the central nervous system (CNS) induces a glial response, in which astrocytes become activated and produce inflammatory mediators. However, the molecular basis for glial activation and the signaling pathways regulating glial/innate immune responses remains poorly understood. Here, we examine the activation of retinoic acid inducible gene-like (RIG) receptors (RLRs) and the involvement of RLR signaling in the regulation of type I IFNs following spinal cord injury (SCI). Immunohistochemical analysis followed by confocal microscopy procedures reveals that astrocytes express two intracellular RLRs, RIG-I and melanoma-associated gene 5 (MDA5). Immunoblotting of spinal cord protein lysates after SCI and stretch injury of culture astrocytes indicates that injury to the CNS activates RLR signaling as determined by phosphorylation of IRF3 leading to production of type I IFNs. Stimulation of RIG-I and MDA5 with synthetic RNA (poly(I:C)) results in RLR signaling activation, phosphorylation of IRF3, and increased expression of glial fibrillary acidic protein and the intermediate filament protein vimentin, two hallmarks of reactive astrocytes. To the best of our knowledge this is the first time that the RLR signaling pathway is described as being involved in regulating astrocyte activation and modulation of the innate immune response after SCI.