A Comprehensive Review of poly(I: C) as a Tool for Investigating Astrocytic TLR3 Signaling

Abstract

Astrocytes play a crucial role in regulating the structure, function, and interactions between the synaptic and vascular compartments in the brain. Toll-like receptor 3 (TLR3) is expressed in astrocytes and recognizes double-stranded RNA (dsRNA), a pathogen-associated molecular pattern (PAMP). This review examines the current understanding of TLR3 signaling, with a focus on its specific role in astrocytes, and the use of the viral mimetic polyinosinic: polycytidylic acid (poly(I: C)) to model the effects of viral infections in both in vitro and in vivo studies. Poly(I: C) is a useful tool for studying neuro-immune communication and has significantly added to our knowledge of how the brain responds to immune challenges. Upon poly(I: C) exposure, TLR3 activation in astrocytes triggers inflammatory signaling pathways, leading to both antiviral responses and neuroinflammation. However, further research is required to investigate the cell-specific impacts of TLR3 activation, along with the influence of developmental stages, brain regions, and sex-specific responses, to gain a comprehensive understanding of how immune activation shapes the development and function of the central nervous system (CNS).