Functional alterations of neutrophils from β-thalassemia patients exposed to Pythium insidiosum: An ex vivo study

Patients with β-thalassemia are highly susceptible to Pythium insidiosum , the causative agent of human pythiosis, a severe and often life-threatening disease in tropical regions. This vulnerability has been associated with iron overload and immune dysregulation. However, the underlying mechanisms of impaired host defense, especially in neutrophils, remain incompletely understood. This study investigated neutrophil function in response to P. insidiosum zoospores, using neutrophils isolated from β-thalassemia patients and comparing their responses with those from healthy controls. Ex vivo study, isolated neutrophils were co-incubated with P. insidiosum zoospores, then evaluated for pathogen-killing activity, neutrophil extracellular trap (NET) formation, and phagocytic capacity. Neutrophils isolated from β-thalassemia patients exhibited significantly reduced fungicidal activity, as indicated by higher fungal burdens in comparison with healthy controls. In addition, NET formation was significantly diminished in the neutrophils isolated from the patient group, reflecting impaired extracellular pathogen containment. Similarly, phagocytic activity in the neutrophils isolated from the healthy group was significantly higher than in the patient group. These findings demonstrate that impairments of neutrophil functions, including killing activity, NET formation, and phagocytic capacity, contributed mechanistically to the increased susceptibility to P. insidiosum in patients with β-thalassemia. This study highlights the importance of targeting innate immune dysfunction in the development of therapeutic strategies for human pythiosis.