The opportunistic pathogenic fungus Aspergillus fumigatus can cause chronic infections in immunocompetent individuals with underlying lung damage, including those with a history of pulmonary tuberculosis (TB) or recurrent TB disease [[1], [2], [3]]. A key feature of TB is formation of granuloma, consisting of necrotic macrophages containing M. tuberculosis (Mtb) bacilli, surrounded by immune cells and infiltrates [4,5]. The liquefaction of the granuloma in the lungs subsequently result in cavity formation. TB-induced lung damage, including cavities, may persist even after a successful TB treatment. Studies have reported elevated anti-Aspergillus IgG levels in symptomatic post-TB patients, particularly those with persistent lung cavities [6,7]. Moreover, A. fumigatus has been documented to complicate active TB in some cases [8,9]. The prevalence of Aspergillus coinfection in pulmonary TB in Asia and Africa is approximately 15.4 %, with A. fumigatus being the predominant species identified [10,11].

A. fumigatus conidia are ubiquitously present in the environment. Upon inhalation, A. fumigatus conidia enter the respiratory tract and interacts with pulmonary epithelium and resident alveolar macrophages [12]. These interactions trigger innate immune responses, with neutrophils and monocytes being recruited to the lungs to eliminate the infection [13]. Simultaneously, antigen presenting cells (APCs) process and present fungal antigens to naïve T lymphocytes in adjacent lymph nodes initiating an adaptive immune response [14,15]. In immunocompetent individuals, fungal conidia are effectively cleared from the lungs. However, in patients with pre-existing lung damage, such as that caused by TB, A. fumigatus conidia may persist and cause chronic infection in the lung. During active TB disease or co-infection of Mtb and Aspergillus, immune cells in the lungs could encounter both pathogens. However, the immune response to these combined stimuli remains uncharacterized. Several pattern-recognition receptors (PRRs), such as toll-like receptors (TLRs), C-type lectin receptors (CLRs), as well as intracellular nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), play key roles in the recognition of both pathogens by innate immune cells [16,17]. Activation of different classes of PRRs by diverse ligands is known to elicit synergistic proinflammatory responses [18].

We therefore hypothesized that A. fumigatus and Mtb may synergistically activate host immune responses. Such heightened inflammatory responses may contribute to persistent inflammation and severe tissue damage. In this study, we investigated how primary immune cells respond to simultaneous presence of these two pathogens. Our findings provide valuable insights into the pathogenesis of Aspergillus co-infection in TB patients and development of post-TB aspergillosis.