Spatial transcriptomic atlas of murine neurotoxocariasis reveals region-specific host responses and dysfunction in the brain
Abstract
Toxocara canis is a globally distributed parasite that infects dogs and other canids, shedding eggs into the environment. Humans become accidental hosts by ingesting these eggs, leading to syndromes such as visceral, ocular and neurotoxocariasis – the latter being poorly understood. Neurotoxocariasis has been associated with epilepsy, cognitive impairment and schizophrenia, but its pathomechanism remains unclear. Here, we combine spatial transcriptomics, single-nucleus RNA sequencing and behavioural assays in a mouse model to characterise the host–parasite interface in the brain. T. canis larvae caused region-specific brain damage, vascular remodelling and confined immune responses. Parasite gene expression was dominated by immunomodulatory excretory/secretory proteins. Infected mice exhibited impairments in motor learning and memory, coinciding with transcriptional changes in neurons and glia. These findings provide mechanistic insight into neurotoxocariasis and demonstrate the utility of the mouse model as a platform to investigate helminth-induced neurological disorders.
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