Immune interaction between Aspergillus fumigatus and non-tuberculous mycobacteria.

INTRODUCTION

The global prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing. Individuals with NTM-PD frequently develop chronic pulmonary aspergillosis, which is associated with poor clinical outcomes. However, the biological mechanisms underlying the interaction between Aspergillus species and non-tuberculous mycobacteria (NTM) remain poorly understood. This study aimed to investigate the interaction between Aspergillus fumigatus and NTM and to identify mechanisms that may inform novel therapeutic strategies.

METHODS

A. fumigatus was incubated with NTM culture supernatants, and biofilm formation was quantified using the crystal violet assay. Phagocytic activity against A. fumigatus conidia were assessed in THP-1-derived macrophages infected with Mycobacterium avium. Conversely, phagocytosis of M. avium was evaluated in macrophages exposed to A. fumigatus culture supernatants. Finally, fungal clearance in vivo was assessed in mice pre-infected with M. avium.

RESULTS

NTM supernatants significantly enhanced A. fumigatus growth. M. avium infection decreased the macrophages-phagocytosis rate of A. fumigatus by approximately 40% compared to uninfected control. Additionally, M. avium infection reduced Dectin-1 gene expression in macrophages by half. Secondary metabolites produced by A. fumigatus impaired macrophage phagocytosis of M. avium. In vivo, prior M. avium infection delayed fungal clearance from the lungs.

DISCUSSION: NTM promote not only A. fumigatus growth but also its colonization by impairing macrophage immune function. Conversely, A. fumigatus suppresses host defense against NTM via secondary metabolites. These findings suggest that microbial cross-modulation creates a permissive niche that facilitates co-colonization and may contribute to disease progression.