Comparative neuropathogenesis of Angiostrongylus cantonensis and Angiostrongylus malaysiensis infection in an experimental BALB/c mouse model

Abstract

Neuroangiostrongyliasis is a neuroinvasive helminth infection caused primarily by the rat lungworm Angiostrongylus cantonensis, which is the main causative agent of eosinophilic meningitis in humans. The closely related species Angiostrongylus malaysiensis coexists in many endemic regions particularly in Asia and Oceania and shares substantial morphological and genetic similarity with A. cantonensis, yet its pathogenic potential remains poorly understood. Here, we performed a direct comparative investigation of neuropathogenesis and host immune responses following experimental infection with A. cantonensis or A. malaysiensis in a murine model. Both species established central nervous system infection and induced neurological manifestations and inflammatory responses. However, infection with A. malaysiensis resulted in more severe clinical disease, characterized by greater weight loss, higher clinical scores, and extensive cerebral hemorrhage, accompanied by increased parasite invasion into the brain parenchyma. In contrast, A. cantonensis infection elicited stronger neuroimmune activation, including increased leukocyte recruitment and elevated expression of type 2 cytokines and chemokines within the brain and meninges. Despite the more severe neurological complications observed in A. malaysiensis infection, immune cell accumulation in the central nervous system was comparatively reduced, suggesting differences in parasite containment at the neuroimmune interface. Together, these findings demonstrate that closely related Angiostrongylus species can induce distinct patterns of neuropathogenesis and immune regulation. Our results highlight the importance of species-specific host–parasite interactions in shaping disease severity and provide new insight into mechanisms underlying the pathogenesis of neuroangiostrongyliasis.