Exploring Neutrophil Heterogeneity and Plasticity in Health and Disease

Neutrophils, the most abundant polymorphonuclear leukocytes, are critical first responders to infection, and have historically been underappreciated in terms of their functional complexity within the immune response. Once viewed primarily as short-lived, innate immune cells with limited functional plasticity, recent research has illuminated their considerable heterogeneity and diverse functional roles, which extend beyond their involvement in steady-state immunity. This review seeks to provide an updated analysis of neutrophil development, maturation, heterogeneity, and plasticity, with a focus on how these characteristics influence immune modulation in both healthy and diseased tissues. Beginning with the origin of neutrophils, we explore their maturation into effector cells and their evolving roles in immune defense under homeostatic and disease-associated conditions. We then delve into their heterogeneity, discussing recent breakthroughs in neutrophil research that challenge the traditional view of neutrophils as a uniform population. We address the significant advances that have been made in identifying distinct neutrophil subsets, the emerging complexities of their plasticity, and the challenges that remain in fully understanding their functional diversity. Finally, we highlight future directions and opportunities for continued exploration in this rapidly advancing field, shedding light on how these insights could open new avenues for therapeutic interventions.