The Triad of Pathogenesis in Allergic Bronchopulmonary Aspergillosis: Interactions among <italic>Aspergillus fumigatus</italic>, Epithelium, and Immunity.

BACKGROUND

Aspergillus fumigatus is a common airborne fungal pathogen responsible for a range of pulmonary diseases, particularly in individuals with pre-existing respiratory conditions. Among these, allergic bronchopulmonary aspergillosis (ABPA) represents the most severe allergic manifestation. It arises from persistent airway colonization by A. fumigatus and repeated immune activation, often leading to uncontrolled respiratory symptoms and progressive lung damage. Despite its clinical relevance, the pathogenesis of ABPA remains poorly understood.

SUMMARY: This review examines the pathogenesis of ABPA, focusing on three major aspects: host genetic susceptibility, persistent airway colonization by A. fumigatus, and an exaggerated type 2 immune response. We discuss how genetic variants affecting immune signaling and epithelial barrier function contribute to fungal persistence, how fungal components disrupt host defenses, and how chronic exposure promotes a T helper 2 (Th2)-skewed immune profile. These interactions between the fungus, airway epithelium, and immune cells drive chronic inflammation, airway remodeling, and irreversible structural damage.

KEY MESSAGES: ABPA arises from a complex interplay among genetic susceptibility, persistent colonization by A. fumigatus, and immune dysregulation. The sustained presence of the fungus is central to both the initiation and progression of disease, while an exaggerated Th2 immune response drives chronic inflammation and airway damage. A deeper understanding of these pathogenic mechanisms is essential to guide the development of more accurate diagnostic tools, effective therapies, and preventive strategies.