From parasite-induced immune activation to neuroinflammation and behavioral dysfunction: convergent mechanisms across protozoa and helminths: a review

Parasitic infections are increasingly linked to persistent neurological and psychiatric sequelae, yet the mechanistic routes from peripheral infection to altered brain function remain incompletely integrated across parasite groups. Emerging work suggests that parasites may influence the central nervous system indirectly through microbiota disruption and chronic immune activation, or directly through neurotropism, ultimately converging on neuroinflammation. Here, we synthesize human and experimental evidence that protozoan and helminth infections can remodel the microbiota–immune–brain axis and promote neuroinflammatory states associated with behavioral dysfunction. Across neurotropic (e.g., Toxoplasma gondii, Plasmodium spp., Trypanosoma spp.) and primarily intestinal parasites (e.g., Enterobius vermicularis, Toxocara spp., schistosomes, and Taenia solium–associated neurocysticercosis), convergent pathways include: (i) sustained peripheral cytokine production and immune-cell reprogramming; (ii) gut dysbiosis with increased microbial products and reduced short-chain fatty acids; (iii) increased intestinal permeability and enhanced immune-to-brain signaling; (iv) blood–brain barrier dysfunction and activation of microglia and astrocytes; and (v) downstream neurochemical and transcriptional remodeling, including perturbations in dopamine/serotonin/GABA-related signaling, indoleamine 2,3-dioxygenase–driven tryptophan catabolism, and infection-associated epigenetic and microRNA changes. Clinically, these cascades are associated with seizures, sleep disturbance, cognitive impairment, mood and anxiety symptoms, and under specific contexts psychosis-like phenotypes. We propose an integrative mechanistic model in which parasite-induced microbiota disturbance and chronic immune activation converge on glial activation and barrier dysfunction to shape brain circuitry and behavior. Defining shared neuroinflammatory nodes across parasitic diseases may reveal tractable biomarkers and host-directed therapeutic strategies to mitigate long-term neuropsychiatric risk.