Neutrophils in Toxocara canis infection: Effector functions, immune evasion and crosstalk with type 2 immunity

Toxocara canis is an important zoonotic parasite with significant clinical relevance to both veterinary and human health. While neutrophils have traditionally been associated with antimicrobial defense, their role as key modulators of immunity against helminths is increasingly recognized. Following infection with Toxocara canis, neutrophils are rapidly recruited through IL-17-mediated signaling cascades, triggered by tissue damage and parasite excretory-secretory products. Despite their several effector mechanisms, including degranulation, reactive oxygen species, and neutrophil extracellular traps, in vitro studies demonstrate that neutrophils are unable to kill Toxocara canis larvae, highlighting the parasite's sophisticated immune evasion strategies. However, in vivo, neutrophils exhibit striking plasticity. They adopt an N2 phenotype via the IL-17/IL-17RA axis. N2 neutrophils are characterized by production of key type 2 cytokines IL-4 and the amplifier cytokine IL-17. This axis plays a dual role; it reduces larval burden by promoting type 2 immune polarization via IL-4 and, simultaneously, amplifies pulmonary inflammation. The outcome of infection reflects a dynamic interplay among neutrophils, eosinophils, and macrophages. Neutrophil-derived IL-17 enhances eosinophil recruitment, whereas IL-4 drives macrophage polarization toward an M2 phenotype that sustains type 2 responses and encapsulates larvae together with other cells. While these interactions restrict larval migration, they also lead to tissue damage, illustrating the trade-off between protection and pathology. Overall, neutrophils in Toxocara canis infection are ineffective at killing the parasite directly, but are important as immunity regulators. Understanding their dual roles provides key insights into host-parasite interactions and can inform therapeutic approaches that strengthen antiparasitic defenses while mitigating immunopathology.