Infection‐Driven Autoimmune Amplification Versus Molecule‐Specific Immune Modulation: The Dual Role of <i>Toxocara canis</i> in Autoimmunity

Abstract

Loss of immune tolerance and sustained inflammatory signalling are central features in the pathogenesis of autoimmune diseases. Although helminth infections are often associated with immunoregulatory protection, accumulating evidence suggests that Toxocara canis may represent an important exception. This review highlights the dual and context-dependent effects of Toxocara canis on autoimmune pathways, where live infection can amplify autoreactivity while parasite-derived molecules exert selective immunomodulatory effects. During acute infection, larval migration induces strong Th1/Th17-skewed inflammation accompanied by tissue injury, autoantigen release, and enhanced antigen presentation, lowering immune tolerance thresholds. Molecular mimicry, polyclonal B-cell activation, and persistent antigenic stimulation may further promote autoantibody production and chronic immune dysregulation. Neuroinvasion and inflammation sustain cytokine networks implicated in disorders such as multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and autoimmune-associated epilepsy. Experimental models of autoimmune encephalomyelitis show that live T. canis infection exacerbates disease severity through amplification of pathogenic Th17 responses. In contrast, parasite excretory/secretory molecules including mucins, C-type lectins, cystatins, serpins and extracellular vesicle cargo, modulate pattern recognition receptor signalling and downstream PI3K/Akt, MAPK and NF-κB pathways. These effects promote regulatory T-cell expansion, alternatively activated macrophage polarization, and anti-inflammatory cytokine production, highlighting parasite-derived molecules as potential templates for targeted immunomodulatory therapies.