The neuro-immune crosstalk between periphery and central nervous system during acute immune response to virus-mimicking RNA in parrots.

Parrots, valued companion animals with a concerning conservation status, can act as reservoirs for zoonotic diseases. During various infections, systemic inflammation significantly impairs host health. However, the regulation of inflammatory responses in birds, particularly in cognitively advanced parrots, remains poorly understood. Here, we examine parrot systemic inflammation in response to virus-mimicking stimulation. In budgerigars (Melopsittacus undulatus), a novel model for neuroinflammation research, we induced sterile inflammation with synthetic poly(I:C) RNA and analysed dose-, time- and tissue-dependent gene expression patterns of key markers, including TLR3, NLRP3, CASP1, IL1B and IL6, during acute immune response. We report a significant relationship between cytokine expression (IL1B, IL6) in the intestine (local response) and brain (systemic response) that has not yet been described after viral stimulation in parrots. Peripheral IL6 expression was upregulated at 3-6 h after stimulation with poly(I:C). In the brain, multiple genes (TLR3, IL1B and IL6) showed activation early during the immune response. These findings highlight the susceptibility of parrots to neuroinflammation following viral infections, having specific relevance for basic research in neurobiology, immunology and behavioural science, and also veterinary research in psittacine birds. Our study provides a foundation for future comparative research on avian neuro-immune crosstalk and neuroinflammation-related behavioural disorders.