Advances in the molecular pathogenesis of Nocardia keratitis

Nocardia keratitis is an infectious ocular disease that poses substantial diagnostic and therapeutic challenges worldwide. It occurs predominantly in individuals with corneal barrier disruption, contact lens wear, or impaired host immunity. Due to its relatively insidious onset, the clinical manifestations are nonspecific, and laboratory diagnosis is technically demanding. As a result, delayed identification and suboptimal treatment are common, often resulting in poor visual outcomes. Although diagnostic and therapeutic techniques have improved in recent years, a comprehensive understanding of Nocardia virulence mechanisms and their complex, dynamic interactions with the host immune system remains to be fully established. Therefore, starting from the temporal sequence of infection and the dynamic host-pathogen interplay, we integrate scattered observations into a pathological framework that traces the transition from colonization to immune dysregulation and ultimately to tissue damage. This review systematically outlines the major virulence factors of Nocardia implicated in the stages of adhesion and colonization, tissue invasion, and intracellular survival. It also discusses the dual role of neutrophils, emerging evidence for pyroptosis, apoptosis, and necroptosis (PANoptosis)-related signaling pathways, and the impact of host immune status on disease susceptibility. This work aims to provide a mechanistic basis for investigating the pathogenesis of Nocardia keratitis, optimizing its diagnosis, and developing targeted therapeutic strategies.