GABAergic system is linked to immune response in dendritic cells infected by Trichinella spiralis

Trichinella spiralis ( T. spiralis ) is a globally prevalent food-borne parasite whose infection triggers robust inflammation and modulates host immunity to facilitate immune escape. Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, is widely expressed in immune cells and regulates inflammation, while dendritic cells (DCs) possess a complete GABAergic system and play a pivotal role in T. spiralis -induced inflammation. However, systematic research on whether T. spiralis infection mediates immunomodulation by acting on the GABAergic system in DCs remains insufficient. This study employed in vivo and in vitro experiments to explore the underlying mechanism. In vitro, cell viability assay, quantitative real-time PCR (qPCR), and Western blotting were employed to detect the toxic side effects, inflammatory response, and impacts of T. spiralis excretory-secretory (ES) products, GABA, and the GABA-A receptor agonist muscimol (Mus) on DC2.4 cells. In vivo, a T. spiralis -infected BALB/c mouse model was established to verify the mechanism. Results showed that ES products regulated DC2.4 cells’ inflammatory factors and GABAergic system in a concentration-dependent and time-dependent manner; GABA and Mus inhibited the TLR4/MyD88/NF-κB pathway, balanced inflammatory and anti-inflammatory cytokines, and exerted anti-inflammatory effects. Pre-gavage of GABA can activate splenic DCs, improve pathological damage, and regulate immune response in infected mice. In conclusion, T. spiralis infection participates in immune regulation by modulating DCs’ GABAergic system, and exogenous GABA or Mus exerts anti-inflammatory effects, providing an experimental basis and new directions for trichinellosis intervention.