Fig. 8.

Schematic overview of the main findings in this study. M.tb exposure to E-ALF from elderly individuals enhances early replication and consequent intracellular growth in ATs. Moreover, AT infection with E-ALF-exposed M.tb alters bacterial endosomal trafficking and increases galectin recruitment suggesting increased endosomal membrane damage driving increased bacterial translocation into the cytosol. E-ALF-exposed M.tb also shows altered production of some inflammatory mediators (cytokines and chemokines) without impacting host cell viability. Overall, A-ALF-exposed M.tb is mainly located in endosomal/lysosomal (vacuoles), whereas; E-ALF-exposed M.tb is located in both vacuolar and cytosolic compartments. In short, exposure to E-ALF promotes M.tb growth within ATs and diminishes AT immune responses, preventing host cell activation and death. E-ALF-exposed M.tb exploits the AT cytosol as a niche for bacterial survival. This illustration was created with BioRender (https://biorender.com/). A = adult ALF-exposed M.tb; ALF = alveolar lining fluid; ATs = alveolar epithelial type cells; E = elderly ALF-exposed M.tb; M.tb = Mycobacterium tuberculosis.