CX3CL1/CX3CR1 involved modulation of microglial activation and eosinophilic meningoencephalitis in angiostrongyliasis.

Angiostrongylus cantonensis typically infects humans through the ingestion of contaminated food or water containing the larvae. A. cantonensis is a neurotropic parasitic nematode that causes eosinophilic meningitis in humans. Upon invasion of the CNS, A. cantonensis larvae elicit a pronounced immune response, rapidly activating microglia and triggering the release of pro-inflammatory cytokines. The CX3CL1/CX3CR1 axis has been implicated in maintaining chronic microglial activation, which could exacerbate neuroinflammation. However, the precise role of this signaling pathway in angiostrongyliasis remains poorly understood. This study aims to elucidate the mechanistic role of CX3CL1/CX3CR1 signaling in microglial activation and neuronal degeneration in CNS infections caused by A. cantonensis. We analyse the expression and downstream regulatory proteins using Western blotting and evaluate neuronal degeneration by Fluoro-Jade C staining in BALB/c mice infected with A. cantonensis. Infected mice showed a marked increase in the expression of Iba-1, CX3CL1, and CX3CR1, indicative of pronounced neuroinflammation. Concurrently, infection led to elevated p-tau accumulation and reduced NeuN expression, suggesting significant neuronal damage. Pharmacological inhibition of CX3CR1 using AZD8797 mitigated these effects by downregulating CX3CL1/CX3CR1 signaling and attenuating neuronal degeneration. Further analysis revealed that the CX3CL1/CX3CR1 axis activates the Nrf2/JNK/HO-1 pathway, contributing to oxidative stress and neuroinflammatory cascades. These findings establish the CX3CL1/CX3CR1 axis as a crucial regulator of microglial activation and neuroinflammation in A. cantonensis infection. Targeting this pathway can offer a viable therapeutic strategy to mitigate inflammation of the CNS and prevent neurodegenerative consequences.