Project

The respiratory tract constitutes a heterogeneous and compartmentalized environment in which biological, chemical, and physical factors shape pathogen evolution, notably that of fungi, in diverse ways. As the primary interface between pathogens and the host, it plays a decisive role in determining whether exposure results in successful clearance, colonization, or progression to invasive infection. In healthy individuals, respiratory fungal infection is uncommon despite continuous exposure to inhaled microbes, owing to the efficiency of multiple host defense mechanisms at the respiratory mucosa. Among these, the coordinated action of mucociliary clearance and innate immune surveillance provides a highly effective barrier, ensuring entrapment and removal of inhaled conidia while preserving pulmonary homeostasis. However, this equilibrium can be disrupted under conditions of impaired immunity. In the context of immunodeficiency, the weakening of host defenses predisposes patients to invasive fungal infections. Conversely, in certain chronic respiratory disorders, fungal colonization of the lower airways is often well-tolerated. For example, in patients with cystic fibrosis (CF), persistent colonization with Aspergilus fumigatus and Scedosporium apiospermum is common. While the presence of these molds now highlighted in the WHO priority list of fungal pathogens may contribute to allergic or inflammatory complications in some patients, in others colonization remains clinically asymptomatic .Early detection of fungal colonization is therefore essential, as lung transplantation remains the ultimate therapeutic option for patients with advanced CF. Despite this, our knowledge of the molecular and cellular processes by which the CF microenvironment shapes the physiology of A. fumigatus and S. apiospermum remains limited, and even less is known about how these environmental changes affect their interactions with the host.