Neutrophils in HIV pathogenesis: dual roles, clinical implications, and therapeutic frontiers

Neutrophils, the most abundant innate immune cells, play a complex role in human immunodeficiency virus (HIV) infection, balancing between protective immunity and pathogenic inflammation. Initially, neutrophils contribute to early viral containment through phagocytosis, reactive oxygen species (ROS) production, and neutrophil extracellular traps (NETs). However, their excessive activation in chronic HIV infection can lead to systemic inflammation, immune dysfunction, and tissue damage. Despite their significance, neutrophils remain underexplored in HIV research compared to CD4+ T cells and macrophages. This review highlights the dual nature of neutrophils in HIV pathogenesis, emphasizing their involvement in immune dysregulation, disease progression, and associated comorbidities such as cardiovascular and metabolic disorders. While NETs can entrap and neutralize HIV, their overproduction exacerbates endothelial dysfunction and inflammation. Additionally, HIV-induced neutrophil dysfunction impairs pathogen clearance, further compromising immune defense. The implications of this review extend to potential therapeutic interventions targeting neutrophil-mediated inflammation. Strategies such as NET inhibitors, antioxidants, and immune modulators could help balance neutrophil function, reducing HIV-related complications while preserving antimicrobial defense. Future research should focus on developing precision therapies that mitigate the detrimental effects of neutrophils without compromising their protective roles, ultimately improving the prognosis and quality of life for people living with HIV.